Wayne Kuznar

Calquence (acalabrutinib) and Rituxan (rituximab) given at a high frequency and low dose demonstrated to be tolerable and effective in patients with previously untreated chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), according to recent results.

All 37 patients enrolled responded to the combination; however, one patient had a complete response (or the disappearance of detectable cancer) but tested positive for minimal residual disease (a small number of cancer cells that remain after treatment; MRD), said lead study author Dr. Danielle S. Wallace in a presentation of the results at the 2021 ASH Annual Meeting.

In addition, she said the regimen has advantages that could prove useful during the COVID-19 pandemic.

“This at-home combination decreased infusion time and patient interactions during the pandemic,” said Wallace, a second-year fellow at Wilmot Cancer Institute at the University of Rochester Medical Center in New York. “This regimen has the potential to enable (Rituxan) to be administered at facilities with limited medical intravenous infusion capacity, which could be very useful in rural and economically disadvantaged areas.”

At a median follow-up of 14 months, 27 patients (73%) have completed at least 12 cycles of therapy. In addition to the one patient (2.7%) with a complete response but positive peripheral blood test, there were 20 partial responses (a decrease in tumor size or the amount of cancer in the body as a response to treatment; 54%) and six partial responses with sustained lymphocytosis (white blood cells; 16%).

“To date, 10 patients have completed 24 cycles, and all were in sustained (partial responses) at the time of their response assessment,” she said. One patient with both a del(17p) and TP53 mutation (often indicative of faster progression of the disease) has had progressive disease following 25 cycles of therapy.

CD20 antibodies such as Rituxan primarily destroy B cells by activating the immune system. Standard doses of Rituxan given at specific intervals may be less effective in CLL than a high-frequency, low-dose regimen because “higher doses result in rapid exhaustion of the finite mechanisms of the innate immune system, via a reduction in phagocytosis and loss of CD20 expression due to trogocytosis,” said Wallace. This means that the immune system is tired from a higher dose due to a reduced ingestion of bacteria and loss of CD20 expression from cells nibbling other cells.

In earlier lines, in which Rituxan was given two to three times a week at lower doses, loss of CD20 was not significant, she said, “supporting further trials of high frequency low-dose (Rituxan).” The subcutaneous (administered under the skin, allowing for slower absorption) dosing of Rituxan that is approved in CLL is more convenient and preferable to patients, allowing the drug to be administered in the patient’s home.

The median age of patients in the trial was 67 years and 60% were men. Patients enrolled were relatively high risk, she said, with 70.2% having at least one high-risk feature, including 21.6% with a TP53 mutation and 13.5% with del(17p).

“While all patients have responded to therapy, no patients to date have achieved an undetectable MRD- (complete response), suggesting that additional agents are required to allow for time-limited therapy,” Wallace said.

Regarding safety, severe side effects occurring in at least 5% of patients included infections (13.5%), neutropenia (low white blood cell count; 8.1%) and anemia (8.1%). The most common side effects were infusion-related reactions (62.1%), infections (56.8%), fatigue (51.3%), anemia (51.3%), headache (43.2%), rash or other skin changes (32.4%), low blood platelet count (29.7%), upper respiratory infections (29.7%), urinary tract infections (18.9%), COVID-19 pneumonia (8.1%), bruising (27%) and diarrhea (21.6%). None of the patients who contracted COVID-19 pneumonia required intubation and all remained on Calquence during their infection.

All infusion reactions occurred during the second hour of infusion, and none required discontinuation of Rituxan. Subsequently, only three patients had injection site reactions with subcutaneous dosing. There were 11 serious side effects, the majority of which were infections. No deaths occurred on treatment.

A version of this article originally OncLive as “

High Frequency Low-Dose Acalabrutinib/Rituximab Combo Elicits 100% ORR in Frontline CLL/SLL

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The combination of Calquence and Rituxan may also be useful during the COVID-19 pandemic as it decreases infusion times and patient interactions, according to an expert.

High-Frequency, Low-Dose Calquence-Rituxan Combo May Elicit Safe Responses in Previously Untreated CLL/SLL

The mRNA COVID-19 vaccine induced a strong antibody response in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), according to observational study results presented during the 2021 ASH Annual Meeting.

Among 46 patients with AML or MDS vaccinated against COVID-19 at Moffitt Cancer Center, 69.6% were seropositive after the first vaccine dose, meaning that COVID-19 markers were found in their blood. This improved to 95.7% after the second vaccine dose, reported Dr. Jeffrey Lancet, at a press briefing delivered during the meeting. Seropositivity indicates that the vaccinated individual is forming antibodies to fight the virus that causes COVID-19.

“Antibody levels increased dramatically following the second vaccine dose, which indicated the potential utility of serial vaccination with good efficacy in poorly responsive patients after the first vaccine dose,” said Lancet, chair of the Department of Hematologic Malignancies at Moffitt Cancer Center.

Antibody titer levels were at a mean of 3,806 after the second vaccine dose, compared with 315 after the first dose, and these levels did not differ between patients with AML or MDS. This difference was observed across different clinical and laboratory variables, including neutropenia, lymphopenia and subsets.

These are promising findings, considering that previous study results have shown that patients with other hematologic malignancies, such as multiple myeloma, 

“Patients with myeloid malignancies, including AML and MDS, based on evolving data, are at high risk of severe COVID-19 infection and death,” Lancet said. “Patients with AML and MDS frequently have quantitative and/or qualitative deficiencies of the white blood cells, including the neutrophils and sometimes the lymphocytes as well, as a result of either the disease itself or the treatment of the disease. It’s unclear whether these deficiencies would result in poor immune response to the COVID-19 vaccine, and to date, there has been very little reported on vaccine efficacy amongst patients with AML and MDS.”

The group of patients with AML or MDS in the study were part of a larger study of the immune response to mRNA-1273 vaccination in all patients with cancer. Of the 46 patients with myeloid malignancies included, 32 had AML and 14 had MDS and were, on average, about two years from diagnosis.

The average age at vaccination for the entire group was 68 years. Patients were vaccinated between Jan. 12 to 25, 2021. More than half of the patients were male (58.7%) and 95.7% were White. The median time from diagnosis to the start of vaccination series was 24.3 months, with a range of 4.5 to 105 months.

Fifteen patients were on active treatment for their disease at the time of vaccination. A total of 32 patients (69.6%) had undergone allogeneic stem cell transplantation (SCT) for their disease. Average time since allogeneic SCT for the entire group was 17 months. Forty patients (87%) were in remission at the time of vaccination. Two patients with AML relapsed post-vaccination.

Blood specimens were collected from patients prior to the first and second vaccine doses (days 1 and 29) and approximately 28 days after the second vaccine dose (day 57) for antibody analyses.

The seroconversion rate — which measures the time between exposure/vaccination and the presence of antibodies — was not affected by age, gender, race, disease status, time to vaccination from disease diagnosis, number of prior lines of therapy, receipt of active therapy at the time of vaccination (including targeted therapies), neutrophil and lymphocyte counts, and transplant history, Lancet said.

“In the patients who did not respond to the first vaccine dose, there were suggestions of patients that had either been on steroid therapy or immunosuppression as potential contributing factors to not converting after the first dose, but just about everybody converted after the second dose,” he said.

Antibody levels were significantly higher in patients with solid tumors in the study after the first vaccine dose compared with patients with AML/MDS, but this difference in antibody response disappeared after the second dose, said Dr. Akriti Jain, a hematology/oncology fellow at Moffitt Cancer Center, during the oral abstract presentation.

The most common side effects following vaccination were mild injection site pain (57.5%), fatigue (40%), headache (25%) and arm swelling (27.5%).

Even though therapy prior to vaccination did not affect antibody levels, the few patients on active treatment included in the study is a potential limitation, Lancet explained. In addition, patients on active aggressive therapy (such as BCL-2 inhibitors) were not included because they were not being vaccinated at that time.

The findings need to be confirmed in a larger and more diverse group of patients, the authors concluded.

A version of this article as originally published on OncLive as, “

Strong Antibody Response to mRNA COVID-19 Vaccine Observed in AML, MDS

Most patients with acute myeloid leukemia and myelodysplastic syndrome achieved strong antibody responses to COVID-19 vaccination, according to recent study results.

mRNA COVID-19 Vaccination Sparks Strong Antibody Response in Patients With AML and MDS

Overall survival in metastatic gas&shy;tric or gastroesophageal junction cancer improved significantly in patients who received the oral combination chemo&shy;therapy Lonsurf (trifluridine/tipiracil; TAS-102), regardless of whether they’d had a gastrectomy (surgical removal of all or part of the stomach).

These results from the phase 3, ran&shy;domized, placebo-controlled TAGS trial were reported by David H. Ilson, M.D., of Memorial Sloan Kettering Cancer Center in New York City. Researchers in 17 countries enrolled patients with inoperable meta&shy;static gastric or gastroesophageal junction cancer that had progressed despite two or more prior chemotherapy regimens. Data analysis included 507 patients, including 221 who’d had prior gastrectomy.

Lonsurf was approved to treat advanced colorectal cancer in 2015. On Feb. 25, 2019, the Food and Drug Admin&shy;istration approved its use in previously treated patients with advanced or meta&shy;static gastric adenocarcinoma, including cancer of the gastroesophageal junction.

Patients treated with Lonsurf lived a median of 5.7 months from the time they started the trial compared with 3.6 months for placebo-treated patients. Median progression-free survival — the time from the start of treatment until the disease progressed &mdash; also improved slightly with Lonsurf, from 1.8 to 2.0 months.

Surgery remains the only treatment with curative potential for early-stage gastric cancer. However, as many as half of patients have recurrent disease, and about 40 percent of those patients have undergone gastrectomy. The research&shy;ers considered many factors that might predict outcomes for patients who took Lonsurf and found that prior gastrectomy was not one of them, Ilson said.

In the overall population and the gas&shy;trectomy subgroup, side effects, particu&shy;larly hematologic ones such as decreased blood counts, occurred more often with Lonsurf. Other reported serious or severe symptoms included decreased appetite (9 percent in the Lonsurf group versus 7 percent in the placebo group), fatigue (7 percent versus 6 percent), lack of energy (5 percent versus 7 percent) and back pain (1 percent versus 2 percent).

Gastrointestinal symptoms of those who took Lonsurf were very infrequent and similar in incidence to those expe&shy;rienced by patients who took placebo. Types and rates of symptoms in patients with prior gastrectomy were similar to those in the study population overall.

“Hematologic side effects, such as neutropenia and leukopenia, may have been somewhat more frequent among TAS-102-treated patients with gastrectomy than in the overall population, but this did not result in more treatment discontinuations,” Ilson said.

Overall survival in metastatic gas&shy;tric or gastroesophageal junction cancer improved significantly in patients who received the oral combination chemo&shy;therapy Lonsurf regardless of whether they’d had a gastrectomy.

After Surgery, Lonsurf Remains Helpful in Gastric Cancer

Patients with previously untreated liver cancer, or hepa&shy;tocellular carcinoma (HCC), lived twice as long if they responded to a tyrosine kinase inhibitor, a type of targeted therapy, compared with patients for whom the drug had little benefit, according to an analy&shy;sis of results from a randomized clinical trial.

Responders to Lenvima (lenva&shy;tinib) or Nexavar (sorafenib) lived a median of 22.4 months versus 11.4 months for patients who did not achieve either a partial or complete response. The analysis considered a variety of factors that could have affected overall survival and identi&shy;fied response to treatment as a way to predict this outcome.

“The association between objec&shy;tive response and overall survival was consistent with results reported in previous studies,” said Masatoshi Kudo, M.D., of Kindai University Faculty of Medicine in Osaka, Japan. “Therefore, patients who achieve an objective response can potentially expect a longer overall survival.” Objective response refers to the pro&shy;portion of patients who experienced a prespecified amount of tumor shrink&shy;age lasting at least a certain amount of time.

Additional studies are needed to validate the association between objective response and survival, Kudo added.

The data analyzed came from the phase 3 REFLECT trial, which compared Lenvima and Nexavar in patients with previously untreated HCC and found that Lenvima was more effective. An analysis of response at two, four and six months showed a significant sur&shy;vival advantage, ranging from five to seven months, for patients who responded to treatment.

Patients with previously untreated liver cancer, or hepa&shy;tocellular carcinoma (HCC), lived twice as long if they responded to a tyrosine kinase inhibitor, a type of targeted therapy.

Wayne Kuznar

High-Frequency, Low-Dose Calquence-Rituxan Combo May Elicit Safe Responses in Previously Untreated CLL/SLL

mRNA COVID-19 Vaccination Sparks Strong Antibody Response in Patients With AML and MDS

After Surgery, Lonsurf Remains Helpful in Gastric Cancer

Targeted Therapy Response Can Predict Survival in HCC, Findings Suggest

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