Karen Blum

Cindy Brown has been in remission since she started taking the immunotherapy drug Tecvayli for multiple myeloma. 

For more than seven years, 58-year- old Cindy Brown of Trabuco Canyon, California, had tried numerous therapies for multiple myeloma, but her disease had always relapsed.

Then, in March 2020, her oncologist at the City of Hope Comprehensive Cancer Center in Los Angeles asked her to consider joining a clinical trial evaluating Tecvayli (teclistamab-cqyv), an immunotherapy drug that is a human bispecific monoclonal antibody, or bispecific T-cell engager, a highly specialized molecule that, by binding to two different proteins, focuses the immune system on two distinct targets to attack the cancer. 

 by binding to both a receptor called CD3 on the surface of T cells and a protein expressed specifically on multiple myeloma cells called the B-cell maturation antigen (BCMA). Brown has been in remission since she started taking the drug.

“It’s been remarkable for me in terms of success. It’s super well-tolerated,” Brown says. “If you met me and didn’t know who I was, you would have no idea I was sick.”

Bispecific antibodies are a type of immunotherapy designed to bring two cells or proteins on a cell together, since proximity helps initiate the immune cascade. Using therapies that specifically recognize a target signal such as myeloma-specific BCMA and act only on those cells “is a much more specific way of targeting the bad cells we’re trying to get rid of, as opposed to therapy that can attack a lot of different types of cells and then cause side effects,” says Dr. Nisha Joseph, an oncologist at Emory Winship Cancer Institute and an assistant professor of hematology and medical oncology at Emory University School of Medicine in Atlanta. “It’s almost like a homing device.”

Only a few such therapies have been approved by the Food and Drug Administration (FDA), generally as fourth-line therapy after other treatments have not worked, and more are in clinical trials. However, study results have been impressive, according to Dr. Krina Patel.

“Heavily pretreated patients who otherwise would have probably not done very well, and [with whom] we would have discussed hospice, are now living longer using these therapies,” says Patel, an associate professor in the department of lymphoma and myeloma at The University of Texas MD Anderson Cancer Center in Houston. “We’re improving overall survival [the time a patient lives following treatment] with these therapies, which is pretty phenomenal.”

Over the past decade, the FDA has approved treatments for multiple myeloma that have had a response rate (patients whose disease responded partially or completely to treatment) varying between 23% and 30%, adds Dr. Joshua Richter, director of multiple myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai and an associate professor of medicine at the Tisch Cancer Institute in New York.

“Now you look at these drugs being used, and the bispecifics are getting 60% to 80% response rates, and some CAR-T (chimeric antigen receptor-T cell therapy treatments) are pushing 90% to 100%. It’s a whole different ballgame,” Richter says.

Take Brown’s case: She first received a diagnosis of multiple myeloma at age 48 after having debilitating leg and hip pain for months. She underwent a chemotherapy regimen of Revlimid (lenalidomide), Velcade (bortezomib) and dexamethasone.

During a three-week break from treatment leading into a planned stem cell transplant, Brown had a nearly complete relapse and had to be admitted to the hospital for three rounds of another seven-drug regimen. At that point, doctors recommended she undergo an allogeneic and autologous stem cell transplant. She had her own bone marrow cells collected and returned to her and also received cells from a donor. The donor cell transplant sent her into heart failure a month later, and she almost died. Finally, she recovered and was in remission for two years.

Brown tried three other therapies before needing radiation treatments because the cancer wasn’t responding. After a short remission, the cancer returned in her arm. As a result, Brown needed surgery to implant a rod from her elbow to her shoulder.

Through the clinical trial, Brown initially received injections of Tecvayli every week for a year, then every other week. She is now receiving injections every four weeks.

“I have not had a detectable cancer marker since I started,” she says.

The FDA approved Tecvayli in 2022 as the first bispecific antibody for use in multiple myeloma.

, a BCMA-CD3-directed bispecific antibody immunotherapy, was approved by the FDA in August 2023 to treat adults with relapsed or refractory multiple myeloma who previously received four or more lines of therapy.

The approval was based on findings from the phase 2 MagnetisMM-3 trial. Among patients who had received four or more prior lines of therapy, the overall response rate (ORR, percentage of patients with complete or partial response to therapy) was 58%, with an estimated 82% of patients maintaining that response for at least nine months.

Among patients whose prior treatment included a BCMA-directed therapy, the ORR was 33%, and 84% of these patients maintained their response to treatment for at least nine months, according to the study findings.

Other anti-BCMA therapies being used for multiple myeloma include the following:

 ADCs contain an antibody that targets BCMA, a chemotherapy agent and a protein that links them together. They work by attaching to cancer cells and delivering chemotherapy directly to those cells. Blenrep (belantamab mafodotin) has been approved by the FDA; it is administered as an intravenous infusion.

: With this option, immune system T cells first are removed from a patient’s blood, and then they are genetically engineered in a commercial laboratory to express a receptor that binds to BCMA. Millions of these CAR-T cells are grown in the laboratory and then infused back into the patient, where they populate the marrow and can stay in the circulation long term, seeking out and destroying cancer cells. CAR-T cell therapy is a one-time therapy, whereas the others require treatments every one to three weeks.

Two therapies approved by the FDA for the treatment of multiple myeloma, 

, are among the CAR-T cell therapies that the agency has requested come with a warning following reports of T-cell malignancies, including CAR-T positive lymphoma, among patients who had been treated with that class of drug, it was reported in January.

Trena Robertson, 51, of Baton Rouge, Louisiana, also has achieved lasting remission with a BCMA- targeted treatment — in her case, CAR-T cell therapy.

Robertson received a diagnosis of multiple myeloma in 2018 after experiencing body pain and having malignant plasma (antibody-producing) cells in more than 90% of her bone marrow.

Trena Robertson received a diagnosis of multiple myeloma after having malignant plasma cells in more than 90% of her bone marrow. 

She first underwent chemotherapy treatments recommended by a local oncologist and then a stem cell transplant at The University of Texas MD Anderson Cancer Center.

She was doing well but started relapsing six months later. By then, Patel, her oncologist, recommended that Robertson enroll in a clinical trial for CAR-T cell therapy as her second line of treatment.

In 2019, Robertson relocated to Houston to start the protocol. She received some injections and had to undergo three rounds of advanced chemotherapy. She made it through the first two rounds but was sick with a fever the first day of the third round. Instead, she ended up in the emergency department in need of a blood transfusion, which meant she had to restart the protocol and chemotherapy a month later.

Later that year, Robertson received treatment with CAR-T cell therapy. She returned home and eventually went back to work as a clinical coordinator for a speech pathology and audiology program at Southern University.

“They told me before the treatment that it was supposed to last anywhere from 18 to 24 months,” she says. “This month makes 47 months that I’ve been in remission. ... I’ve been doing very well.”

Selecting the appropriate treatment for each patient depends partly on availability and access, according to oncologists. Because CAR-T treatment regimens are made specifically for each patient and only two therapies are approved for multiple myeloma, there are limited slots available, and the products take several weeks to manufacture. Patients who are frail or can’t tolerate some of the side effects of bispecifics may be better candidates for ADCs, Patel says.

The side effects of CAR-T cell therapy and bispecifics include cytokine release syndrome (signs of systemic inflammation such as fever, chills and drops in oxygen or blood pressure), which is likely associated with the activation of T cells, says Dr. David Avigan, director of the Beth Israel Deaconess Medical Center Cancer Center and a professor of medicine at Harvard Medical School in Boston.

Other reactions include neurotoxicity, which can cause seizures but usually responds to steroids, or a temporary suppression of blood counts, which can increase the risk of infection. Blenrep, the ADC, can cause ocular side effects such as blurred vision or dry eyes. 

Some patients have expressed fear over the ocular side effects, Joseph says, but they shouldn’t. Studies have shown that with treatment these side effects completely resolve in nearly all patients. Symptoms vary and can be mild.

“Patients can tolerate this drug and have quality of life. That’s important because sometimes I feel like I have to convince someone to take it, where the other option is hospice care,” Joseph says.

When Brown started the trial, she spent just under two weeks in the hospital with cytokine release syndrome and says she had increased pain in the areas of her body that had active myeloma at the time.


“But after probably four treatments, I didn’t get that anymore,” she says. “Occasionally at the injection site, I get a little rash that itches for a couple of days. But that’s sort of sporadic. It’s very well tolerated. ... I get the shot and I leave.”

She receives monthly infusions of intravenous immunoglobulin proteins to help fight infections, has laboratory tests every two weeks and has a PET scan every three months. She has some mild symptoms akin to an upper respiratory infection and says she feels a little tired but overall is doing well.

Robertson experienced a fever within the first 24 hours of receiving her CAR-T cell therapy. “They said that was good because it meant the treatment was doing what it was supposed to be doing,” she says.

She has since been monitored with blood and urine testing, as well as periodic PET scans and bone marrow biopsies.

Some questions remain about the use of anti-BCMA therapies. Could the therapies be used earlier on? Can these therapies be administered one after the other if needed, such as giving a bispecific after CAR-T cell therapy? The predominant thought is that T cells could be exhausted after their first round of therapy, but data published by Richter’s group demonstrated that may not be the case. Some patients who received CAR-T cell therapy or a bispecific, and then received another T-cell engager as their next line of therapy, did better than patients who received other types of therapies as the next line.

“It turns out you can reinvigorate and reactivate those T cells sequentially,” Richter says.

Other concerns are whether myeloma cells will adapt and shut off the expression of BCMA to evade therapy, as well as how best to manage infections and alert doctors regarding symptoms to watch.

Much of the science is focused on trying to understand the mechanisms of resistance and how to get around them, Avigan says, as well as how to prevent cells such as CAR-T cells from being rejected. Similar to how oncologists initially used chemotherapy to simultaneously give different drugs that work in different ways, combination immunotherapies may emerge to help avoid pathways of resistance by targeting different pieces of the immune system, Avigan says.

And so, research continues. Other promising agents in the pipeline include the bispecific antibodies linvoseltamab, which is being developed by Regeneron, and ABBV- 383, which is being developed by AbbVie, Patel says.

For now, oncologists are focusing on BCMA as the primary target, but there are others being studied, such as G-protein coupled receptor family
C group 5 member D (GPRC5D) and Fc receptor-like protein 5 (FcRH5).

“[With] the more knowledge we accrue, is there a magic combination we can use to start curing [patients] on a regular basis? I’m hopeful we can,” Richter says.

Articles

The BCMA protein has become the primary target for treating multiple myeloma, resulting in longer survival and more manageable side effects.

A 'Whole Different Ballgame' for Myeloma Treatment

When Stacy Deems received a diagnosis of breast cancer in September 2019, her first concern wasn’t about her health, it was how she would afford treatment. The divorced mother of two teenaged boys worked for a nonprofit organization with a basic health plan.

“When I brought up (costs) to the oncology team, they were like, ‘You don’t have to worry about that. We’ll discuss it later,’ ” says Deems, 51, of Reisterstown, Maryland. “That’s not how my brain works. I need to know.”

Stacy Deems initially covered costs with the help of family and friends. 

In an initial conversation with the office manager, Deems discovered that although she likely didn’t earn enough to afford her medical bills, she made too much money to qualify for some grant programs. So, she got to work: Deems ensured her doctors all were in the network covered by her health plan and focused on her out-of-pocket maximum cost because she knew she would hit it.

She met with an insurance counselor at the hospital, who recommended a different plan to choose and advised her to get short-term disability insurance in case she needed it. She also used a flexible spending account to cover some bills and medications.

Deems also told family and friends about her plight. Over the past several years, as she underwent chemotherapy and radiation, a mastectomy and reconstructive surgery, she changed jobs and health plans, a family member covered her out-of-pocket maximum costs, and she found other sources of assistance, such as a copay card from her pharmacy. She followed up on any leads for organizations providing grant assistance.

“I just realized I can’t be shy or proud, and I need to just ask for everything and look for any free services that I could get because of what I’m fighting,” she says.

Deems’ financial concerns are common among patients with cancer, says Dr. Fumiko Chino, a radiation oncologist at Memorial Sloan Kettering Cancer Center in New York City whose research is focused on affordability and patient costs. Financial toxicity, a term used to describe financial problems and stress caused by medical costs, affects anywhere from 15% to 65% of patients, she says.

Each person’s financial impact will look unique from factors including the type of cancer they have, what their insurance will cover and the complexities of their treatment plan. 

“If you need chemotherapy and surgery and radiation, you’re going to generally be at a bigger risk for financial toxicity than if you just needed one of those treatments,” Chino says. Costs can add up both from medical and medication expenses as well as from lost income if people have to miss work.

Chino personally understands the patient and family perspective on cancer costs. Her late husband, Andrew, died from a neuroendocrine cancer in 2007. At the time, his insurance company would cover up to half a million dollars in expenses for a lifetime, which his treatment easily exceeded. At one point, he interviewed for and accepted a different job just to have a new health insurance plan, she said, yet she was still left with debt after he died. The experience inspired her to switch careers from art to medicine.

There are several ways to lessen financial costs, says Daniel Sherman, an oncology financial navigator at a Michigan hospital, and president of the NaVectis Group, an organization that trains health care providers on patient financial navigation services.

Ideally, discussions about cancer finances should begin on the day
of receiving a diagnosis, before any treatments occur, says Sherman: “The earlier that a well-trained financial navigator can get involved, the easier it is to mitigate not all but a lot of the financial distress that patient is going to experience.”

When Sherman sits down with patients, he first assesses the person’s insurance coverage to see if there are any opportunities for insurance optimization, or plan adjustments. Often this can happen outside of traditional open enrollment times, especially if there will be a decrease in income due to the diagnosis or if a patient falls below 150% of the federal poverty level.

Beyond that, there are several other resources where patients can receive assistance. Nonprofit hospitals all have charity programs where patients could qualify for free or reduced care. Pharmaceutical companies often have patient assistance programs to help cover drug costs. A variety of patient assistance foundations exist that help cover assorted medical costs, transportation to treatment and other items such as wigs for those who lose their hair.

Out-of-pocket costs for Health Insurance Marketplace plans, which are plans run by the federal government for individuals, families and small businesses, cannot exceed $9,100 in one calendar year, he says. For members of Medicare Advantage plans, those costs cannot exceed $8,300. For people covered by commercial insurance plans or Medicare Advantage plans, these out-of-pocket maximums are not uncommon.

Some people think they’re not going to qualify for assistance, so they don’t even ask. “That’s a mistake. There is no harm in asking. Most people qualify for something,” Sherman says.

Another myth is that patients who ask about financial assistance will receive substandard care. “Nothing can be further from the truth,” Sherman says. “Financial toxicity, left untouched, does more harm to people than asking for assistance.”

Apply for financial assistance as soon as it is necessary; don’t wait until bills have piled up and treatment is over, advises Joanna Doran, an attorney and the chief executive officer of Triage Cancer, a nonprofit organization that provides free education on practical and legal issues impacting people with cancer and their caregivers. “In some cases, you might lose out on eligibility for assistance, because some programs will only provide assistance while you’re in treatment.”

There aren’t specific federal laws that protect patients from medical bills, Doran says. However, the three major credit reporting agencies as of July 2022 have agreed not to include paid medical debt on people’s credit reports.

Always review medical bills carefully before paying them, Doran says: “It’s a human process, and a large percentage of medical bills have errors.” 

Individuals should compare their bills against the explanation of benefits (EOB), a statement from their health insurer that lists what medical services they had, how much the plan pays for them and what charges are not covered.

“Sometimes providers send bills too quickly, before they’ve actually gotten payment from the insurance company,” she says. If individuals pay before comparing to the explanation of benefits, they might pay more than they are actually responsible for.

Once individuals know for sure what they owe, and notice that the figure is too high, they should communicate with their provider, Doran says. See if they can set up a payment plan, or if the provider will accept a lump sum payment at a lower amount. Those scenarios are common, especially at larger hospitals. 

If individuals need additional assistance, then look into financial assistance through the hospital or other nonprofit organizations. “Most people jump to financial assistance, and the challenge with that is if you haven’t figured out what you actually owe, then you’re worrying about paying a bill you might not owe,” Doran says. “There’s only so much financial assistance to go around, so we want to make sure that people are maximizing their ability to get those funds.”

One big issue contributing to financial toxicity is denials, where an insurance company denies coverage for medical care or services. Only 0.1% of people with Marketplace plans appeal those denials, Doran says, but when they do, and it gets to an external medical review process where an independent party reviews the company’s decision, they are successful about 50% of the time.

Scott Matsuda, 69, of Mountlake Terrace, Washington, and his wife, Jennifer Matsuda, have become experts at navigating the finances of cancer treatment. Scott Matsuda was diagnosed approximately 16 years ago with thrombocytosis, a blood disorder in which the body produces too many platelets. But his doctor told him it could turn to leukemia, and a year later, it did.

After participating in a clinical trial, Scott Matsuda found out that his twice-a-day medication would cost $104 per pill. 

The first thing Scott Matsuda did was review his family’s finances and contact his insurance company. As photographers who run their own business, the Matsudas purchased the best health plan they could afford to cover Scott Matsuda’s medical costs. For several years he took a cocktail of medications and had minimal copays. Then he started experiencing side effects and doctors switched him to a new, more expensive medication.

For the first three months, Scott Matsuda qualified for a clinical trial and received the drug for free. When the trial ended, he discovered the medication cost about $104 a pill, and he needed two pills a day. His health plan would only cover about 20% of the charges.

“We were floored with the cost and didn’t know how to pay for it,” Scott Matsuda recalls. “We’re solid, middle-class people. We pay our bills and have really high credit ratings, and suddenly, everything was going to blow up in our faces.”

“It was over $6,000 a month, and the options for us were don’t take it, knowing this might be a lifelong drug, or sell the house and drain your retirement account,” adds Jennifer Matsuda.

He stopped taking the drug, which sent his platelets skyrocketing. Then, his oncologist connected the Matsudas with the PAN Foundation, an independent nonprofit group that helps cover medication costs for people living with chronic and rare diseases. They qualified for a copay grant that covered the medication for a year at a time.

Three years ago, Scott Matsuda needed a bone marrow transplant, which he received from his sister. By then he was old enough to qualify for Medicare, which covered most of the cost. Now in remission, he is back on the expensive drug to combat graft-versus-host disease. But before he started taking it, Jennifer Matsuda contacted the pharmacy, which told her they had some grants available to cover the medication. Scott Matsuda is now receiving funds from his fourth grant foundation to help pay for the medication, leaving him with copays averaging $200 a month.

“There’s a whole community of organizations out there that provide different aspects of care and support and help,” Scott Matsuda says. “That’s a revelation when you start going down that avenue.”

As for Deems, she currently has no evidence of disease but is on a maintenance medication and receives mental health services for the trauma and post-traumatic stress disorder brought on by her diagnosis and surgeries. She covers those expenses with pretax dollars through a flexible spending account.

For more news on cancer updates, research and education, don’t forget to 

Healing should be the primary focus of patients and survivors. But for many, the effects of high medical costs can become a burdensome challenge. Care providers, experts and family work to provide assistance.

The Financial Toxicity of Cancer Treatment

KAREN HANNA says it was interesting to be on a clinical trial testing a maintenance therapy she would later be prescribed. 

Karen Hanna was first diagnosed with ovarian cancer in April 2013. At the time, she underwent a debulking (tumor burden reduction) surgery and received chemotherapy. 

Then her oncologist asked if she would like to enter a clinical trial testing a new type of drug called a PARP inhibitor, which her doctor hoped would become maintenance treatment one day. Hanna gladly volunteered.

By the time Hanna’s cancer recurred in November 2018, her oncologist had good news: the maintenance therapy was now approved by the Food and Drug Administration (FDA) and she would be eligible for it following another round of surgery and chemotherapy. She started the treatment, called Lynparza (olaparib), in February 2020.

She first heard about the potential for maintenance treatment in 2013. 

“I didn’t think much about it because I was just in survival mode,” says Hanna, now 50 years old, of Oklahoma City. “It’s kind of interesting that you’re in a clinical trial for a PARP inhibitor in hopes (it) will show that maybe it will be of benefit one day as maintenance therapy. And seven years later, you’re using it as maintenance therapy.”

Maintenance therapy is given after a patient completes chemotherapy to decrease the chance that the cancer will come back or to delay it from recurring, explains Dr. Kathryn P. Pennington, an assistant professor of obstetrics and gynecology at the University of Washington in Seattle.

“It’s given to continue or maintain the good results of a prior treatment,” Pennington says. “The idea behind it is that it is often better tolerated than traditional chemotherapy, so it’s something that someone could be on for a long time and feeling well, while hopefully delaying the cancer coming back.”

Maintenance therapy is an option for women with stage 2, 3 and 4 cancers that respond well or very well to surgery and platinum-based chemotherapy, according to the National Comprehensive Cancer Network (NCCN). 

Options for therapy depend on whether a person has a germline (inherited) mutation in the BRCA1 or BRCA2 gene or if their tumor is considered homologous recombination deficiency (HRD) positive, meaning the tumor is unable to repair double-strand breaks in DNA and is determined by gene sequencing characteristics. Options also depend on whether a person’s primary chemotherapy regimen included Avastin (bevacizumab).

Two types of targeted therapies are used in this setting. Avastin works by inhibiting vascular endothelial growth factor (VEGF), a protein that helps cancer grow blood vessels for food and oxygen. And PARP inhibitors that stop cancer cell DNA from being repaired by a protein called PARP, so that damaged DNA stays at a level that causes cells to trigger their own death, constraining tumor growth. Three PARP inhibitors are approved by the FDA for ovarian cancer: Lynparza, Rubraca (rucaparib) and Zejula (niraparib).

Depending on the drug, patients should receive maintenance therapy for 15 months to three years. The goal is to stop, says Dr. Kathleen Moore, the Virginia Kerley Cade Endowed Chair in Cancer Development and a professor of gynecologic oncology at the University of Oklahoma College of Medicine in Oklahoma City.

“Patients who have evidence of disease, and (for whom) you’re holding things stable, … need to continue for as long as they’re receiving benefit,” she says. “But for patients who are in a complete response, I do think it’s important to stop, because some of those patients may not recur ever, or for many years.” 

Additionally, there is a sense that continuing on a PARP inhibitor could lead to a less robust response to subsequent chemotherapy if cancer recurs, Moore notes.

The rationale behind maintenance therapy is based on two principles, according to Dr. Robert L. Coleman, chief scientific officer at US Oncology Research, in Woodlands, Texas. One is that as many as 20% to 30% of patients will have a recurrence of their cancer in a short period of time following treatment, even if it doesn’t initially show up on biomarker tests or imaging studies, he notes.

“Many years ago, we used to assess the quality of the initial response by operating,” says Coleman, who is also a gynecologic oncologist at Texas Oncology. The procedure is called second-look surgery. “When we looked for cancer in patients who didn’t have any other overt evidence of disease, we would ultimately find residual disease in about half the patients. So we knew this strategy probably wasn’t very sensitive or specific with respect to the disease being gone.”

A second principle is that maintenance therapy, when used to prevent cancer recurrence, also can shrink tumors if it’s active against cancer or has anti-cancer activity, Coleman adds. “Patients are getting even deeper responses while they’re taking the therapy, so in that context, maintenance is actually a form of additional treatment,” he says.

Hanna says her experience on Lynparza since February 2020 has been positive, and she has tolerated the therapy well.

“I might have had a little fatigue up front,” she says, but she remembers telling her doctor at the four-month mark that it didn’t feel as though she was taking anything. “I try and take very good care of myself,” she adds. “I exercise six days a week, I eat very healthy (foods). I’m very mindful about living a healthy lifestyle.” 

She also has a busy career in pharmaceutical sales and serves on boards of directors for different organizations. “I’m going and going and going all of the time. So if I am experiencing fatigue from this pill, I don’t know it.”

February 2022 marked her two-year check-in being on maintenance therapy. Her scans and blood markers looked good enough that her oncologist wanted her to remain on the treatment for one more year. If she continues to do well, she’ll then stop therapy.

Hanna is one of thousands of women who have done well on maintenance therapy. For such patients who have a mutation in either the BRCA1 or BRCA2 gene, maintenance therapy medications are “extremely effective,” says Pennington.

For example, investigators of a clinical trial called SOLO-1, which evaluated Lynparza after primary treatment for patients with BRCA1 and BRCA2 mutations, found that the drug delayed cancer recurrence by more than 40 months at the median. It also lowered the risk of cancer progression or death by 70% compared with a placebo, she says.

Other trials also have demonstrated benefits of the therapies. Results from the PRIMA study, which examined Zejula in patients who had responded to platinum-based chemotherapy, showed that the drug delayed disease progression for people with BRCA1 and BRCA2 mutations by 11 months compared with placebo. 

The drug delayed cancer progression by a similar length of time among patients who did not have a mutation but whose tumors had HRD. In contrast, the drug delayed cancer progression among people who had tumors without BRCA1/2 mutations or HRD by just three months.

KIM BELL says that the severe fatigue caused by her maintenance therapy has forced her to cut back on her business.

Kim Bell, 58, of College Station, Texas, started maintenance therapy with Lynparza and Avastin in February 2022. Bell was treated for stage 3 ovarian cancer in 2021 and had surgery followed by six chemotherapy treatments. She had an Avastin infusion in early February, with repeat infusions every three weeks, and takes Lynparza pills twice a day. 

®, she was scheduled for imaging tests to see how well the treatment was working.

Her experience has been a little different from Hanna’s.

Lynparza “causes severe fatigue for me since I’m taking 600 (milligrams) a day,” says Bell, who has had to cut back a bit on her floral design business due to her lack of energy. 

“After periods of rest or sitting, it takes me a few steps to move normally since it is affecting my joints and muscles a great deal, as well as my back. My doctor and specialty pharmacist indicated that many patients see side effects subsiding after a couple of months, and I’m only two months in to taking the drug. I generally don’t have any side effects from my (Avastin) infusions.”

Although she says she doesn’t want to quit the therapy because of the potential benefits, she notes she plans to ask her doctor about reducing the dose to see if that helps. That option had been presented to her during discussions before starting the therapy.

Fatigue, nausea, vomiting and low blood cell counts are among the most common symptoms with Lynparza, according to the NCCN. Anemia or myelodysplastic syndrome, a cancer in which the bone marrow does not make enough healthy blood cells, are rarer.

Patients “feel like a wet noodle,” Moore says. “They’ll say over time they accommodate to it and they’re able to do everything they want to do, but they do feel this level of fatigue that is real and needs to be acknowledged.” 

Despite that, “their quality of life, even though they may have more side effects, does not appear to be diminished,” Coleman notes, “so it seems to be what we could call a tolerable regimen.”

As the science continues to evolve, oncologists are looking forward to additional or refined treatments including combination therapies. HR proficient tumors is one area ripe for improvement, Pennington says. 

“It would be ideal to find a maintenance therapy where we could do better than that three months’ magnitude.”

Another concern is what to do with patients whose cancer recurs even after treatment with PARP inhibitors, she adds. Should they be prescribed PARP inhibitors again? Are there ways to restore PARP resistance? Could the inhibitors be combined with another chemotherapy or medication to make it sensitive to PARP inhibition again? 

This is an area of active study, says Pennington, investigating combinations of PARP inhibitors with other drugs, such as agents that inhibit the ATR protein or those that block the growth of blood vessels that support tumor growth. Analysis of tumors that recur after PARP inhibition may be able to reveal specific alterations that could inform new therapies.

“Even in patients who are really good candidates for a therapy, we find some who still have recurrence and progression,” Coleman says. “Better treatments are always going to be an unmet medical need for our patients.”

There are potential opportunities for additional maintenance therapies using a newer class of drugs called antibody-drug conjugates, he notes, especially among patients that don’t have BRCA 1/2 mutations. 

Some of these are in clinical trials launching now, Moore points out. “There’s probably going to be a lot of development in this space moving forward.”

For now, Hanna says she encourages patients to give maintenance therapy a try. 

“This is the biggest breakthrough for ovarian cancer in decades, and one that is showing very promising outcomes … and extending the lives of ovarian cancer patients, which is huge,” she says. “Embrace it, don’t be afraid of it. The odds of you being able to tolerate this are in your favor. … Go into it knowing that this is something that can hopefully get you to the next best option that is coming in the future.”

She also encourages patients to stay positive and to believe that “your mind is your greatest weapon.” Staying in a positive and grateful framework makes a difference, she says, “I truly believe that.”

Bell agrees. Hearing from her doctor that her body could adjust to the medications, making the side effects more tolerable, “gave me hope that at least there’s a light there and I can work toward that light, push through, and get there.”

Although maintenance treatments have helped patients with ovarian cancer live longer, experts note there are still some unmet needs that must be addressed. 

Maintenance Therapy the 'Biggest Breakthrough in Decades' for Ovarian Cancer

Michael Kimbarow was 13 years old in 1966 when he received a diagnosis of Hodgkin lymphoma. Doctors surgically removed a tumor within the parotid (salivary) gland on the left side of his face and applied radiation treatments to the area. He was then considered cancer-free and went on to live his life.

Nearly 40 years later, Kimbarow was working as a professor of communicative disorders and sciences at San Jose State University in California when one day, the left side of his face started to droop and became paralyzed.

A series of tests revealed a secondary cancer — a parotid tumor, which doctors thought was a late effect of the radiation he had received decades before. In contrast to the lymphoma that originated from lymphocytes in the parotid gland area, the second cancer arose from the parotid gland cells, likely induced by radiation.

“I was really just devastated to hear that I had another cancer,” says Kimbarow, now 69, “and I didn’t know at that point what all of the implications were.” But he continued to work while undergoing treatment, and a year later underwent reconstructive surgery to restore some facial symmetry.

Kimbarow’s experience is not isolated. Nearly 1 in 5 cancers diagnosed today occurs in an individual with a previous diagnosis of cancer, according to the National Cancer Institute.

The term “secondary cancers” can be confusing, explained Dr. Stephanie Schaub, an assistant professor of radiation oncology at the University of Washington in Seattle. She usually describes them to patients as “new and different tumors caused by treatments,” such as radiation, chemotherapy or targeted therapy. “That helps just emphasize to patients that it’s not their (original) tumor coming back.”

Treatments such as radiation or radioactive iodine (for thyroid cancer) are one known cause of secondary cancers. Chemotherapy can later 

. The hormonal therapy tamoxifen, used to treat breast cancers, increases the risk of developing uterine cancer later on. Despite associations such as these, the benefits of cancer treatment far outweigh the risk of developing secondary cancers, according to experts.

However, not all secondary cancers are caused by earlier treatment. Other risk factors include 

family history, or genetic predisposition

. Certain racial and ethnic groups, such as Ashkenazi Jews, have a higher prevalence of mutations to the BRCA1 and BRCA2 genes associated with breast, ovarian and pancreatic cancers. People with a family history of ovarian cancer may be at higher risk of developing the condition, too, as genetic mutations can be inherited. Some secondary cancers are unrelated to the initial cancer.

Age also plays a role. People like Kimbarow who are first diagnosed with cancer as a child or adolescent, or under age 45, are at a higher likelihood of experiencing a secondary cancer later, as the risk of cancer increases with age.

Exposure to environmental pollutants such as cigarette smoke is also a contributing factor. And some cancers themselves promote a higher risk of secondary cancer. People with chronic lymphocytic leukemia and non-Hodgkin lymphoma, for instance, have a higher than normal risk of developing other cancers such as skin cancers, says Dr. David A. Bond, a hematologist at The Ohio State University Comprehensive Cancer Center in Columbus.

Overall, a decrease in the immune system associated with the initial cancer can increase the risk of developing a secondary cancer, explains Dr. Jennifer A. Woyach, a hematologist-oncologist at Ohio State. This is especially true in cases where the epithelium, the lining of the body’s tissues, is damaged, such as skin cancers associated with damage caused by ultraviolet light.

In general, secondary cancers take at least three to five years to develop, but the majority are seen years to decades after the initial diagnosis of a patient’s original tumor, Schaub says. The risk can depend on many factors such as younger age, genetic predisposition and treatments given for the original tumor.

If it’s genetic, each gene has its own peak in incidence for secondary cancer, mentions Dr. Siddartha Yadav, a breast and gynecologic cancer specialist at Mayo Clinic and an assistant professor of oncology at Mayo Clinic College of Medicine in Rochester, Minnesota.

Adding complexity, it may not always be easy to tell if a new cancer that develops is related to treatment for the first cancer, says Schaub.

The biggest indicators are the type of new tumor that develops, coupled with the prior therapies received. If a teenager with Hodgkin lymphoma is treated with radiation to the chest and later develops a breast cancer within the area that received radiation, the new cancer is likely linked to treatment. However, no pathologic or genetic studies are available to date to prove the association between new and prior cancers, she explains.

That’s the case for Mary Lou Smith. Smith, who is over 70 and lives in the Chicago area, has survived three types of cancer. She received a diagnosis in her early 40s with early-stage ductal carcinoma in situ (DCIS) breast cancer and had a second DCIS 21 years later.

Smith had ovarian cancer about eight years after the second breast cancer, followed by colon cancer three years later. The breast and colon cancers were detected through routine screenings, and the ovarian cancer was found based on Smith reporting symptoms. After myriad treatments and follow-ups, Smith is considered as having no evidence of disease (NED). Two types of genetic testing found nothing to suggest she is at risk of developing cancers, but Smith finds it hard to believe she doesn’t have some genetic predisposition.

“When I got a second breast cancer, I was really angry,” she says. “In my head, I had done that … I was moving on. With the ovarian cancer, I was very frightened. I knew that was lethal, and by the time it’s found there’s not much to do except a lot of treatment. … With the colon cancer, I was just irritated to be honest. Like, 

Cynthia Chauhan says she took her secondary cancer as a sign to do new things. She left her job as a clinical social worker and took up rock climbing, drawing and painting.

Cynthia Chauhan, too, has had several bouts with cancer. Her first cancer was detected in 1998, when she was hospitalized for a surgical procedure and started having significant pain. Imaging tests revealed a tumor in the center of one of her kidneys. Cancer specialists at Mayo Clinic, where she was seen, surgically removed the kidney and continued to monitor her.

Three years later, while waiting to undergo a routine mammogram, Chauhan thought about an aunt who had died from inflammatory breast cancer. The next thing she knew, Chauhan herself was sitting down with a radiologist to discuss the findings, which had identified a DCIS breast cancer.

“It was scary,” says Chauhan, now 79, of Wichita, Kansas. “I (already) had been through a pretty rough sequence with the kidney cancer.” But she mentions she was not overwhelmed by the diagnosis because she felt she was in a good medical center for treatment and care.

Chauhan took her secondary cancer as a sign to do new things. She left her job as a clinical social worker and took up rock climbing, drawing and painting.

“Those are ways that allowed (me) to see myself differently,” she explains, and they enabled her to support herself emotionally while going through radiation treatment.

She also used visualization techniques, calling on her love of gardening. She began thinking of her breasts as a beautiful garden of flowers that had been invaded by a weed that needed removal. Today her status also is considered NED.

Kimbarow, Chauhan and Smith all say their doctors didn’t talk to them about their risk of developing secondary cancers. Cancer still had a lot of stigma attached to it in the 1960s, Kimbarow says: “It was still kind of whispered about. So we really didn’t talk too much about it.”

Smith recalls seeing information about secondary cancers in reading material given to her about the carboplatin and paclitaxel drugs she was prescribed for ovarian cancer.

“By that time it was like, ‘Oh well, what do you want me to do about that? I want to live today, so I’ll take a chance on five years down the road,’” she relates.

Fortunately, times are changing. Woyach and Schaub note that they discuss the risks of secondary cancer with their patients during the initial visit.

“I think sometimes people have this impression like, ‘I already have one cancer, so I don’t need to worry about something else. I have enough on my plate,’” Woyach says. “But it’s really important to continue other recommended, age-appropriate screenings.”

Depending on the type of treatments given, there may be adjusted screening recommendations to allow for earlier detection and/or prevention of secondary cancers, explains Schaub.

Throughout the cancer journey, whether secondary or primary, support and self-advocacy are crucial, Chauhan and Smith note.

“It’s important to have a caregiver who is very supportive and to understand that you are the most important person in your cancer care team,” Chauhan says. “You have a right and almost a responsibility to advocate for yourself, … to ask questions and to expect to get meaningful, understandable answers to those questions, and then to really focus on how you can best take care of yourself as you go through this.”

For example, back when Chauhan’s physician told her he was 98% sure she had kidney cancer and wanted her to schedule surgery the next day, Chauhan asked to hold off so she could do her own research, make a list of questions and have all her concerns answered before the procedure. “The surgeon reluctantly agreed,” she says.

Smith added her own advice: Make sure you attend all appointments for treatments and follow-up care and keep track of your health. “It is important to know your own body. If you feel there’s something
that isn’t going the way it should, then tell someone.”

Secondary cancers generally are diagnosed based on a patient’s symptoms or routine screenings and follow-up care. Oncologists monitor some cases more closely, Yadav points out, such as for patients who receive chemotherapies known to be associated with second cancers or who receive PARP inhibitor drugs associated with blood-based cancers.

Some secondary cancers identified early, such as skin cancers, are more likely to be curable and can be screened for easily, Woyach explains. But blood cancers such as myelodysplastic syndrome or acute leukemia tend to be more subtle and come on slowly, and don’t have as many screening tests.

Treatment for secondary cancers generally is the same as for primary cancers, but there are times when oncologists have to consider additional options. Prior cancer therapies may have limited a patient’s reserves to tolerate a full dose of radiation therapy, Schaub says, or make it more difficult to perform surgery in a particular area. Chemotherapies also may be limited. One routinely used in breast cancer called doxorubicin should only be prescribed as a limited dose over a lifetime, according to Yadav. If a patient develops a secondary cancer for which the standard of care would be giving them the same drug, it becomes challenging.

“Really, it does become an individualized, thoughtful approach to patient care,” Schaub says. “There’s definitely no exact textbook (recommendation) for how to treat them.”

Kimbarow has been taking anti-cancer medications off and on since 2018 for lung tumors thought to be a metastasis from his 2006 parotid tumor. But he doesn’t worry about it or let it slow him down, saying he has two mantras: “The first is that I refuse to stop living before I die. And the second is that I’ve yet to read any scientifically peer-reviewed study that shows or demonstrates that sitting in a dark room feeling sorry for myself will improve my outcome. Until I do, there’s no point in it, so I just move forward day by day and enjoy it.”

Although no surefire way exists to prevent the development of subsequent cancers, cancer survivors can take steps to boost their health. Most important, mentions Woyach, is to undergo any recommended cancer screenings. Any young woman who had radiation to the chest under the age of 30 should be screened twice a year for breast cancer beginning eight years after completing radiation, using MRI and mammograms, notes Bond. Survivors of chronic lymphocytic leukemia and low-grade lymphomas should undergo skin cancer screenings at least annually, he says.

Also understand that if a patient has a genetic profile that increases their chance of developing a secondary cancer, they should be screened, Yadav says. If they haven’t had genetic testing, Yadav recommends they ask their oncologist if that might be right for them.

If there are no related genetics or family history, patients are advised to control other lifestyle and environmental factors. Experts advise patients the following: don’t smoke; limit sun exposure and use sunscreen; eat a healthy diet; increase consumption of fruits, vegetables and other vegetarian foods; and decrease consumption of meat.

Exercising also may reduce the recurrence of cancers, Yadav explains. “This can be just walking around … it does not have to be full cardio exercise, but it should be a minimum of one hour, three to four times a week,” he advises.

Cancer researchers are continuously working to develop newer treatments with fewer side effects while also trying to understand their association with risks for developing secondary cancers. Proton therapy, a newer form of external beam radiation therapy that minimizes radiation to healthy tissues surrounding a tumor, or immunotherapies that reinvigorate the body’s natural immune system to fight cancer eventually may be affiliated with fewer secondary cancers.

Research in breast and other cancers focuses on the genetic risk of developing secondary cancers, Yadav says. He also notes that over the past 20 years or so, scientists have found that genes such as ATM, CHEK2 and PALB2 cause breast cancer and are associated with secondary cancers. Current studies are looking to pinpoint what an individual’s risk is and what factors can modify that risk. Other studies are focused on the nature of secondary cancers and potential prevention.

“Right now, our recommendations are saying, ‘OK, if you’re genetically predisposed to developing ovarian cancer, we need to take the ovaries out,’” Yadav explains. “But are there other ways beyond doing surgeries? It’s not quite (at the point) where we can take certain medications and prevent secondary cancers … but that’s the goal.”

Kimbarow’s attitude has been so positive that his oncologist featured him as one of three patients in a talk on people who didn’t give up and showed remarkable response to treatment.

“Don’t stop living before your body gives out on you,” Kimbarow says. “You never know what the next therapy is that’s right around the corner. … The advances in science are amazing.”

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Although certain cancer treatments have been linked to an increased risk of a secondary cancer years later, an expert notes there are no genetic or pathologic studies that prove the association between new and previous cancers.

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