June 2013, Vol 4 No 4

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Advances in Bendamustine Clinical Trials

Colleen Ross, RN, MSN, MHA, OCN

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Bendamustine is currently approved for the treatment of chronic lymphocytic leukemia (CLL), and many ongoing studies are investigating its efficacy in drug combinations. Data in the relapsed/refractory setting are promising regarding improved overall survival and manageable toxicities, such as reversible myelosuppression, nausea, and fatigue – nursing implications mandate careful patient monitoring and management of these adverse effects. To this end, knowledge of the toxicity profile of bendamustine and combination therapy will improve patient outcomes.

Lymphoid Malignances
Therapy with bendamustine and rituximab in CLL has demonstrated efficacy in the relapsed/refractory setting. The most common adverse effect was myelosuppression, in the form of neutropenia, anemia, and thrombocytopenia.1 Twenty-one clinical trials are currently ongoing for patients with CLL. Other trials include combinations such as bendamustine, rituximab, and fludarabine. Using the combination of alemtuzumab and bendamustine for a patient population in which 84% were previously treated with fludarabine, an overall response rate (ORR) of 70% was reported, including a 26% complete re­sponse (CR) and 44% partial response (PR) rate.2

Indolent and Mantle Cell NHLs
Seventeen ongoing clinical trials are investigating the use of combination therapy in indolent non-Hodgkin lymphoma (NHL) and mantle cell lymphoma (MCL). Bendamustine plus rituximab is approved for use in the first-line setting for the treatment of MCL. Compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), bendamustine and rituximab resulted in longer progression-free survival (57.2 vs 30.9 months in patients achieving PR).3 Another study presented at the 2012 American Society of Hematology Annual Meeting investigated bendamustine versus R-CHOP/R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone).4 Again, the ORR was impressive: 94% for bendamustine and rituximab versus 84% for R-CHOP/R-CVP. In the MCL group, bendamustine and rituximab resulted in a significantly higher CR rate than did R-CHOP/R-CVP (51% vs 24%; P=.018). Other combinations under investigation include bendamustine, rituximab, and bortezomib; idelalisib (GS-1101) plus rituximab and/or bendamustine; and bendamustine plus ofatumumab. A bendamustine, rituximab, and cytarabine combination has been studied in patients in the first-line setting, relapsed and refractory. These patients did not qualify for an autologous stem cell transplant (ASCT). Promising results were shown with an ORR of 100% in treatment-naive patients, including a 95% CR rate. In patients with relapsed/refractory disease, ORR was 80%, with a 70% CR rate.5

Aggressive NHL
Eight trials are ongoing trials for aggressive NHL. At the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting, bendamustine plus rituximab presented efficacy in relapsed/refractory diffuse large B-cell lymphoma. These pa­tients were ineligible for ASCT. During the 2010 ASCO Annual Meeting presentation, ORR reported was 58%, in­cluding a 19% CR rate.6

Other Malignancies
Combination therapies with bendamustine are in clinical trials for other disease sites as well. Current trials for Hodgkin lymphoma are investigating bendamustine coupled with drugs such as lenalidomide, gemcitabine, and brentuximab vedotin. Sixteen clinical trials are ongoing for multiple myeloma (MM). For newly diagnosed patients with MM receiving either bendamustine/prednisone or melphalan/prednisone, ORR was 75% versus 70%, respectively, and a significantly higher number achieved CR with bendamustine (32% vs 13%; P=.007).7 In addition, maximum response was noted to be faster in the bendamustine arm. Other studies include bendamustine/bortezomib/prednisone in patients who are compromised renally, and a conditioning trial of bendamustine and melphalan for patients undergoing bone marrow transplant. Solid tumor ongoing treatment studies include non–small cell lung cancer, metastatic breast cancer, and sarcoma.

Summary
Bendamustine, either alone or in combination therapy, has proven to have efficacy in lymphoma and CLL. As clinical trials continue, we hope in the near future to see treatment protocols that are effective, minimize toxicities, and help improve patient outcomes and quality of life. Clinical trial information is an important part of educating our patients, empowering them to choose among treatment options. Clin­ical Web sites, such as www.clinicaltrials.gov, are a good resource for patients to access information on current trials and locations.

References
1. Fischer K, Cramer P, Busch R, et al. Bendamustine combined with rituximab in patients with relapsed and/or refractory chronic lymphocytic leukemia: a multicenter phase II trial of the German Chronic Lymphocytic Leukemia Study Group. J Clin Oncol. 2011;29:3559-3566.
2. Tedeschi A, Rossi D, Coscia M, et al. Final report of bendamustine and alemtuzumab (BEN CAM) combination in relapsed and refractory chronic lymphocytic leukemia. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 2898.
3. Rummel MJ, Niederle N, Maschmeyer G, et al. Subanalysis of the StiL NHL 1-2003 study: achievement of complete response with bendamustine-rituximab (B-R) and CHOP-R in the first-line treatment of indolent and mantle cell lymphomas results in superior survival compared to partial response. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 2724.
4. Flinn IW, Van der Jagt RH, Kahl BS, et al. An open-label, randomized study of bendamustine and rituximab (BR) compared with rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP) or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line treatment of patients with advanced indolent non-Hodgkin’s lymphoma (NHL) or mantle cell lymphoma (MCL): the Bright study. Blood (ASH Annual Meeting Abstracts). 2012;120. Abstract 902.
5. Visco C, Finotto S, Zambello R, et al. Combination of rituximab, bendamustine, and cytarabine for patients with mantle-cell non-Hodgkin’s lymphoma ineligible for intensive regimens or autologous transplantation. J Clin Oncol. 2013;31:1442-1449.
6. Vacirca JL, Acs PI, Shimkus BJ, et al. Bendamustine/rituximab in relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol. 2010;28(suppl). Abstract 8041.
7. Ponisch W. Mitrou PS, Merkle K, et al; East German Study Group of Hematology and Oncology (OSHO). Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone — a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006;132:205-212.

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