Hayley Virgil

The drug combination of Lynparza (olaparib), Zytiga (abiraterone) and prednisone led to better progression-free survival outcomes and responses compared to either Lynparza or Zytiga alone plus prednisone, according to findings from a phase 2 study presented at the 

Of note, progression-free survival (PFS) is the time patients live without their disease getting worse.

The study included several arms: patients in arm 1 received Zytiga and prednisone; arm 2 received 300 mg of Lynparza; and arm 3 received 300 mg of Lynparza plus Zytiga and prednisone.

The median PFS was 39 months in arm 3 compared with 8.4 months in arm 1 and 14 months in arm 2.

The combination of Lynparza, Zytiga and prednisone demonstrated better outcomes in terms of progression-free survival and response rates compared to using Lynparza or Zytiga alone along with prednisone.

A total of 33% of patients in the combination arm responded to treatment — a higher percentage of those in the Lynparza/prednisone and Zytiga/prednisone arms.

The prostate-specific antigen (PSA) response rate in the combination arm was notably higher at 95% compared to 61% in the Zytiga/prednisone arm and 67% in the Lynparza arm. Additionally, the rate of undetectable PSA was 33%, 17% and 14% in the combination, Zytiga/prednisone, and Lynparza arms, respectively.

The study involved 165 patients with metastatic castration-resistant prostate cancer, and the combination therapy showed manageable side effects, with grade 3 side effects affecting 19% of patients in the combination arm, 21% in the Zytiga/prednisone arm and 14% in the Lynparza arm. Common grade 3 side effects included anemia and fatigue.

Additionally, the objective response rate (ORR; percentage of patients whose disease shrunk or disappeared from treatment) in each respective arm was 33%, 2%, and 14%. Moreover, the prostate-specific antigen (PSA) response rate in arms 3, 1 and 2, respectively, was 95%, 61% and 67%. The rate of undetectable PSA was 33%, 17% and 14%.

A total of eight patients crossed over from Zytiga/prednisone to Lynparza, and eight crossed over from Lynparza to Zytiga. The median PFS from crossover was 8.3 months with crossover to Lynparza and 7.2 months with crossover to Zytiga. Additionally, the median PFS from randomization was 16 months and 16 months. The ORR to and PSA response rate to crossover treatment was 38% and 25%, as well as 50% and 63%, respectively.

“2023, as you are all aware, was a really dynamic year for the PARP pathway,” lead author Dr. Maha Mussain, the Genevieve E. Teuton Professor of Medicine at Northwestern University’s Feinberg School of Medicine, said in a presentation on the data. “The FDA approved the combination of Lynparza and (Zytiga)/prednisone for frontline patients with castration-resistant disease and BRCA1/2 alterations. “

To be included in the study, patients needed to have an mCRPC diagnosis and no previous exposure to PARP or androgen receptor inhibitors or chemotherapy, washout of antiandrogen for metastatic hormone-sensitive prostate cancer, radiation and other investigational agents. Those who enrolled received next-generation sequencing and germline testing. Those with inactivating BRCA1/2 and/or ATM alterations were randomly assigned to one of the three arms. Those in arms 1 and 2 were able to cross over to Lynparza and Zytiga/prednisone, respectively, upon progressive disease.

The study’s primary end point was radiographic PFS, with key secondary end points including ORR, PSA response rate and toxicity.

A total of 165 patients were included in the study and received somatic/germline testing. Of these patients, 61 were randomly assigned to arms 1 to 3, including 19 in arm 1, 21 in arm 2, and 21 in arm 3. The median age in each respective cohort was 63, 68 and 69. Additionally, the baseline PSA in each respective group was 14 ng/mL, 14 ng/mL and 15 ng/mL. Patients in each respective cohort had bone metastases (84% versus 57% versus 76%), lymph node metastases (47% versus 57% versus 48%) and visceral metastases (11% versus 14% versus 33%).

In total, 47% of those in arm 1, 62% in arm 2 and 52% in arm 3 had germline alterations, and 53% versus 38% versus 48%, respectively, had somatic mutations. The most common genetic mutation was BRCA2 (68% versus 90% versus 71%, respectively).

“(In terms of) declines from baseline (PSA) to the lowest PSA, the combination arm does better than the single-agent arm,” Hussain noted.

Grade 3 side effects impacted 21% of patients in arm 1, 14% in arm 2 and 19% in arm 3. Common grade 3 side effects in each arm, respectively, included anemia (0% versus 4.8% versus 4.8%) and fatigue (5.3% versus 4.8% versus 4.8%).

Among those who crossed over to receive Lynparza and Zytiga/prednisone, respectively, one patient in the latter arm experienced grade 3 hyperglycemia.

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Lynparza, Zytiga and prednisone led to improved progression-free survival and response rates in patients with metastatic prostate cancer. 

Lynparza Plus Zytiga Boosts PFS, Response Rates in Metastatic Prostate Cancer

Treatment with Kymriah (tisagenlecleucel) showed responses lasting more than three years in patients with relapsed/refractory follicular lymphoma, according to data from the phase 2 ELARA study that were presented at the 

2023 American Society of Hematology (ASH) Annual Meeting and Exposition

According to the Food and Drug Administration, Kymriah is a genetically modified autologous T-cell immunotherapy drug that targets a protein called CD19 in patients with relapsed/refractory follicular lymphoma.

The CAR-T cell therapy, Kymriah, led to lasting responses in patients with relapsed/refractory follicular lymphoma. 

A total of 81 responding patients (54%) maintained a response at the data cutoff. The likelihood of remaining in response 33 months following the first response was 63% for complete/partial response to treatment and 73% for complete response. Additionally, the likelihood of patients beginning a new treatment at 36 months following Kymriah was 35% in the efficacy evaluable population of 94 patients.

There were 98 total patients enrolled in the ELARA study and who underwent Kymriah manufacturing with the possibility of bridging therapy with chemotherapy.

A total of 97 patients underwent infusion with Kymriah and 94 were evaluated at the first efficacy assessment at month 3 after restaging and lymphodepletion (treatment to reduce the population of circulating lymphocytes) in patients who received bridging therapy. The study had a median follow-up of 40.6 months.

To be included in the study, patients were required to be 18 years of age or older with grade 1 to 3A relapsed/refractory follicular lymphoma. There also needed to be no evidence of histologic transformation/FL3B or prior treatment with anti-CD19 therapy or allogeneic hematopoietic stem cell transplant (a procedure when a patient receives healthy stem cells from a donor).

The study’s primary endpoint (the main result measured at the end of a study to see if treatment worked) was the complete response rate (no signs or symptoms of cancer because of its response to treatment).

The study’s key secondary endpoints included overall response rate (ORR; percentage of patients who show a partial or complete response to treatment), duration of response (DOR; length of time when a tumor responds to treatment without worsening) and progression-free survival (PFS; length of time during and after treatment when a patient’s cancer does not worsen).

Secondary endpoints from the study also included overall survival (OS; length of time from diagnosis or start of treatment when a patient is still alive) and safety.

Data from the study indicated that the median PFS was 37 months with a median follow-up of 30 months.

Additionally, the 36-month PFS rates in the overall population and those with a complete response to treatment were 53% versus 69%, respectively. The median OS among those treated with Kymriah was not reached, and the 36-month OS rate was 82%.

Researchers reported that neither the DOR nor the time to the next treatment was reached at a median follow-up of 41 months.

The median patient age was 57 years. Bulky disease was present in 64% of patients. Additionally, 63% of patients experienced progressive disease at 24 months following the first anti-CD20 monoclonal antibody-containing regimen.

There were 68% of patients who were double refractory to an anti-CD20 monoclonal antibody and alkylating agent. Patients also had several comorbidities at baseline, including cardiac disorders (16%), diabetes (10%) and renal insufficiency (poor function of the kidneys due to reduced blood flow; 8%).

It was reported that rates for PFS and OS at 36 months were consistent for patients who experienced progressive disease at 24 months and those without. Specifically, the 36-month PFS rate was 50% in those with progressive disease at 24 months and 59% in those without. The corresponding OS rates in each respective group were 83% and 80%.

Researchers also reported that high baseline levels of peripheral CD8-positive, naïve T cells correlated with long-lasting PFS and DOR.

“(These findings) were consistent with previously reported data from other very early studies in smaller datasets,” according to lead author Dr. Stephen J. Schuster, during a presentation on the findings. “Those patients who had a higher concentration of naïve T-cells, in particular CD8-positive naïve T-cells, were associated with having a prolonged PFS or DOR relative to those who had lower levels.”

Schuster — the director of the lymphoma program and lymphoma translational research, as well as a Robert and Margarita Louis-Dreyfus Professor in chronic lymphocytic leukemia and lymphoma clinical care and research at Penn Medicine — emphasized that those who had not experienced progressive disease at 24 months had a higher mean CAR transgene expansion and more durable persistence.

Responses and durations did not differ among the progressive disease at 24 months subgroups, despite expansion differences; CAR transgene persistence was reported up to 1,290 days.

Schuster indicated that there were no new findings regarding safety. The most common high-grade toxicities any time after infusion were neutropenia (low levels of white blood cells; 43%) and anemia (19%).

Frequent serious side effects included cytokine release syndrome (CRS; an aggressive response to immunotherapy drugs; 20%), pneumonia (11%), and febrile neutropenia (fever during a period of having low levels of white blood cells; 8%).

To date, a total of 18 patients died during the study, with eight dying due to progressive disease, nine due to side effects, and one to euthanasia. Side effects resulting in death included metastatic squamous cell carcinoma, encephalitis (brain inflammation), pneumonia, bladder transitional cell carcinoma, acute myeloid leukemia, infection, CRS, gastrointestinal hemorrhage and cardiac arrest.

Researchers reported long-lasting responses and no new safety concerns in patients with relapsed/refractory follicular lymphoma during the 2023 ASH Annual Meeting and Exposition.

Kymriah Elicits Long-Lasting Responses in R/R Follicular Lymphoma

A three-drug regimen was safe in treating patients with newly diagnosed myeloma, recent research showed. 

Darzalex (daratumumab) Kyprolis (carfilzomib), Revlimid (lenalidomide) and dexamethasone — a combination known as Dara-KRd — followed by consolidation double transplant in patients with high-risk, newly diagnosed multiple myeloma proved to be safe and efficacious in the phase 2 IFM 2018-04 study, according to final results presented at the 2023 International Myeloma Society Annual Meeting.

The complete response (CR; percentage of patients whose disease completly disappeared after treatment) rate/stringent CR rate after the second autologous stem cell transplant (ASCT) was 81%, according to the protocol analysis. Additionally, the minimal residual disease (MRD) negativity rate, which describes a state in which there are no residual cancer cells detectable on a blood test, at the same time point was 94%.

Lead author Dr. Cyrille Touzeau, a hematologist in the Department of Hematology at the University Hospital of Nantes, Frances noted that response rates continuously improved during the study.

Touzeau also reported that the progression-free survival (the time from random assignment in a clinical trial to disease progression or death; PFS) rate was 86% at 24 months and 80% at 30 months. Additionally, the 24-month and 30-month overall survival (time from treatment until death of any cause; OS) rates were 94% and 91% respectively. In total, eight patients progressed, and seven died due to both disease progression and serious side effects

“Dara-KRd plus double transplant induced deep response rates and a high MRD negativity rate,” Touzeau said during a presentation on the findings. “…These favorable results are in accordance with the GMMG CONCEPT trial for our German Colleagues. The safety and efficacy profile of anti-CD38/KRd plus double transplant support this intensive approach for high-risk patients based on MRD positivity in our IFM phase 3 MIDAS trial.”

The trial included patients who were under 66 years old with newly diagnosed, transplant-eligible multiple myeloma that is high risk with an ECOG performance status of 0 to 2, meaning that they ranged from being able to perform all their daily tasks independently to needing some help with daily tasks. The trial’s primary end point was getting over 70% of patients to second transplant, with key secondary end points including safety, overall response rate, PFS, OS and stem cell collection.

The median patient age was 57 years (range, 38-65). A total of 8% of patients had extramedullary disease and all patients had high-risk cytogenetics. Additionally, 60% of patients had two or more high-risk cytogenetic abnormalities.

As of this update, 56% of patients were receiving ongoing treatment, and 42% had discontinued due to stem cell collection failure, progressive disease, side effects and withdrawal. Although stem cell collection originally took place after cycle six, the study protocol was later amended to take place after cycle three. It was reported that 16% of patients were unable to proceed to tandem transplant because of insufficient stem cell collection.

In terms of hematologic side effects, common any-grade events included neutropenia (48%), anemia (34%) and thrombocytopenia (36%); these were also the most common grade 3/4 events (44%, 22%, and 24%, respectively). Frequent any-grade non-hematologic side effects were infection (64%), gastrointestinal (GI) disorders (62%) and peripheral neuropathy (20%), with grade 3/4 side effects including infection (14%) and GI disorders (10%).

A  low rate of high-grade blood-related side effects following treatment with induction Dara-KRd and consolidation double transplant was discovered in a trial for patients with high-risk, newly diagnosed multiple myeloma.

Three-Drug Regimen Is Safe for Newly Diagnosed Myeloma

Health insurance — among other factors — can play a role in the survival of patients with blood cancer, recent research showed. 

Factors including insurance coverage, economic status and marital status can affect survival outcomes and health disparities for patients with blood cancers, according to findings presented at the 2023 Society of Hematologic Oncology (SOHO) Annual Meeting.

Researchers analyzed survival outcomes and health disparities in patients with blood cancers based on five factors: lack of access to health insurance, treatment at a non-academic facility, low income, low education level and unmarried status. The researchers then compared several subgroups of patients with blood cancers with the overall population and found that there were improvements for survival, but health disparities were growing.

In a population of 57 patients, the outcomes evaluated in the included studies were overall survival (period from diagnosis or treatment where patients are still alive), early mortality, cancer-specific survival (period from treatment initiation to patient death from cancer), progression-free survival (period during and after treatment of cancer when the disease does not worsen) and disease-free survival (period after the end of cancer treatment when a patient survives without signs of that cancer).

Several types of blood cancers were included in the review of 24,353 patients, including Hodgkin lymphoma, non-Hodgkin lymphoma and Burkitt lymphoma; multiple myeloma and polymyositis; acute myeloid leukemia, acute lymphocytic leukemia and myelodysplastic syndrome; and chronic myeloid leukemia and chronic lymphocytic leukemia.

Results demonstrated that insurance status was significantly associated with survival, with similar findings regarding facility type. Researchers also found that provider expertise and marital status both played a significant role in survival as well.

When assessing the impact of economic stability and education, income had a significant association with survival outcomes. Similar findings were reported concerning high school education. Employment and ninth grade education were not significantly associated with survival. Poverty was considered insignificant when all factors were analyzed together vs. not significant in 50% of patients.

“When we compare those (survival) curves with the overall population of the United States, we can see that those improvements have not reached everybody,” Marisol Miranda-Galvis, research project manager at Georgia Cancer Center, said during a SOHO presentation on the analysis. “There are obvious reasons that could explain those differences, but our interest is to identify what those actions are that clinicians could implement in clinical practice, regardless of limitations, that could help to close that gap.”

Investigators defined social determinants of health (SDH) as a “set of non-biologic factors that shape the environment of daily life that influence health outcomes.” Such factors included access and quality of education, access and quality of health care, social and community context, economic stability and neighborhood/built environment. The goal of the analysis was to identify the SDH that have been assessed with regard to their impact on outcomes and determine which SDH were linked with worse treatment-related outcomes.

SDH that were evaluated were health care access (53.%), including insurance status (47.1%) and facility type (28.5%); economic stability (25.0%), including income (81.8%) and poverty (12.1%); education access (14.4%), including high school education (94.7%); and social context (7%), including marital status (100%).

Several economic stability and education factors in 33 and 19 patients, respectively, were also associated with a survival disadvantage, including having a lower income and education level. The impact of poverty rate appeared inconclusive, while no significant correlations were observed from unemployment rate and ninth grade education level.

When looking specifically at health care access in 70 patients and social context in 10 patients, Miranda-Galvis shared several key takeaways.

“In terms of health care access, this domain was evaluating insurance status; those with Medicaid, Medicare and who were uninsured had lower survival rates compared with those with private or military health coverage,” she said. “In terms of facility type where the patients were treated, those who didn’t receive treatment at an academic institution or research institution presented with a (worse) mortality compared with those who received treatment at community, comprehensive or integrated cancer centers.”

Survival outcomes and disparities for patients with blood cancers may depend on factors including insurance coverage, economic status and marital status. 

Hayley Virgil

Lynparza Plus Zytiga Boosts PFS, Response Rates in Metastatic Prostate Cancer

Kymriah Elicits Long-Lasting Responses in R/R Follicular Lymphoma

Three-Drug Regimen Is Safe for Newly Diagnosed Myeloma

Survival for Patients With Blood Cancers May Depend on Social Factors

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