CHICAGO—A small Phase II trial of bendamustine plus rituximab as second-line therapy for diffuse large B-cell lymphoma (DLBCL) reported here at the ASCO Annual Meeting showed an overall response rate of 58% and a complete response rate of 19%.
Bendamustine is approved in the United States for treatment of relapsed B-cell follicular low-grade non-Hodgkin’s lymphoma, but its activity in aggressive lymphomas is not known.
The data, presented in a poster-discussion session, were from the first 26 of 38 patients accrued in the trial. First author Jeffrey L. Vacirca, MD, Chief of Clinical Research at North Shore Hematology Oncology Associates in East Setauket, NY, who reported the results, said that the patients, all CD20+, had relapsed disease after initial therapy for DLBCL and were not eligible for autologous stem cell transplantation, the preferable treatment regimen, because of comorbidities or advanced age. These patients generally have a poor prognosis.
Current front-line therapy for most patients with DLBCL is R-CHOP, with response rates typically between 70% and 90%, Dr. Vacirca explained, adding that about 50% of those patients go on to a long-term response.
“But that means that up to half of patients who respond end up having a relapse, and we have some alternative for them.”
The median age of the patients in the study was 75, and participants were evenly divided between men and women.
The regimen includes six 28-day cycles, with rituximab at 375 mg/m2 on Day 1, and bendamustine at 120 mg/m2 on Days 1 and 2. The data were for a median of three cycles per patient.
“Bendamustine offers a therapeutic option for patients with relapsed disease who would otherwise be given significantly more toxic treatments, all of which are infusional and require hospitalization,” Dr. Vacirca said, listing EPOC (cyclophosphamide, doxorubicin, prednisone, and vincristine); D-HAP (dexamethasone, cytarabine, and cisplatin); RICE (rituximab, ifosphamide, carboplatin, and etoposide); and E-SHAP (etoposide, cytosine, cisplatin, and methylprednisone).
He said the majority of trial patients had received one line of initial therapy, although about one-quarter of the patients had received two, three, and even four lines of treatment. Four patients on the trial had had autologous stem cell transplant and then subsequently relapsed.
Dr. Vacirca said the previously transplanted patients had the same response rate in the trial as the other patients.
While long-term maintenance with chemotherapy but without stem cell transplant is being tested in other hematologic diseases, Dr. Vacirca said the concept is “not ready for prime time yet” in relapsed DLBCL patients.
“The standard still is to transplant those patients who are able to go through a transplant and who meet the criteria. But at least for patients who relapse subsequent to transplant, or for patients who are not transplant-eligible, this is an alternative that’s not as toxic as what we’ve historically given.”
The duration of response is not available from this trial yet, Dr. Vacirca said, but a new DLBCL trial is under way comparing the bendamustine-rituximab combination as first-line therapy versus R-CHOP.
“We’re about a year into that trial, and we anticipate accrual of the trial by the end of this year, and then to have data out by next year’s ASCO.”
Dr. Vacirca’s colleagues on the trial were from Gainesville (Florida) Hematology Oncology Associates; Austin (Texas) Cancer Centers; and Tower Cancer Research Foundation in Beverly Hills, California. The trial was sponsored by Pharmatech in collaboration with Cephalon.
Discussant: “Results a Bit Surprising”
The Discussant for the session, Nancy L. Bartlett, MD, Associate Professor of Medicine in the Medical Oncology Section of Washington University in St. Louis, said the results were “a bit surprising to us, since [bendamustine’s] approval is for low-grade lymphomas.”
She said when the first single-agent study of bendamustine in DLBCL in 2002 showed a relative response rate of 44%, “bendamustine didn’t make much of a splash then because we weren’t familiar with it and didn’t have access to it.
“But now that it’s approved for follicular lymphoma and is the new standard of care, I think we’ll see a lot more studies in non-Hodgkin’s lymphoma as well.”
Dr. Bartlett said the regimen is a reasonable option for patients not eligible for transplant or who are failing to respond to the transplant, because “there are so few therapies and this treatment is so well tolerated and can be given for an extended period time.”
She said most patients in that setting probably need to stay on bendamustine-rituximab therapy indefinitely as long as they are tolerating it.
“I think there also needs to be consideration for incorporating [this regimen] earlier in treatment, maybe as second line before transplant instead of for relapse after transplant,” she said.
Higher Bendamustine Dose
A noted hematologic malignancy specialist not involved with the trial noted that the 120 mg/m2 bendamustine dose in this study is higher than the 90 mg/m2 usually used when it is combined with rituximab for follicular or for indolent lymphomas.
Asked for his opinion for this article, Frederick B. Hagemeister, MD, Professor of Medicine in the Department of Lymphoma/Myeloma at the University of Texas MD Anderson Cancer Center, said, “It’s interesting they were able to get really decent overall response rates and almost a 20% CR rate, which is very valuable. It means this regimen is something that could be used to treat patients.”
Dr. Hagemeister questioned, though, why the trial was open only to patients not eligible for transplant: “I would think this regimen could also be used in transplant-eligible patients, not just patients for whom there is no other really great option of therapy,” he said.
He said that while bendamustine-rituximab was associated with a significant drop in neutrophils and a small drop in platelet count, overall he would consider it a safe regimen—”This is a trial that needed to be done to evaluate them.”
Dr. Hagemeister said it was understandable that only 26 of the 36 patients in the intent-to-treat population had at least one response evaluation.
“It’s not surprising that 10 patients dropped out early, most of them because they had progressive disease early on,” he said, adding, though, that he would like to see whether the patients who dropped out were refractory or responsive to therapy.
And he said he would want to see the results by various demographics, including what first-line regimens patients had and whether they were responsive or refractory.
“Who knows?,” he said. With further investigation, “this might lead ultimately to a registration for large-cell lymphoma.”