Combination Therapy of Bortezomib with Low-Dose Bendamustine in Elderly Patients with Advanced Multiple Myeloma.

Bortezomib has been approved for recurrent or therapy-resistent multiple myeloma in 2003. There is growing evidence that combination therapy of bortezomib with other agents considerably improves results (Richardson P, ASH 2004). Bendamustine is an alkylating agent widely used in Germany for treatment of multiple myeloma and indolent lymphoma. There is no cross-resistance to other alkylating agents. Weekly low dose application is well tolerated and highly effective in elderly patients with pretreated indolent lymphoma (Bremer K, ASCO 2003, Abstract 2410).

Treatment modalities: We treated 17 pts (8 female, 9 male, median age 70 yrs (range 51–82) with relapsed multiple myeloma. Previous therapies ranged from 2 to 7 (median 4), and included 15 x thalidomide, 2 x tandem high dose melphalan, 2 x bortezomib/dexamethasone.

Therapy regimen: bortezomib 1 – 1.3 mg/m² d 1,4,8,11; bendamustine 60 mg/m² d 1+8, dexamethasone 3x8 mg orally d 1–3 and d 8–10: ondansetrone 8 mg intravenously d 1,4,8,11. Cycles were repeated q3w until best response. The median number of cycles applied was 4 (range 3 – 6).

Results: Outcome was evaluated according to SWOG criteria.

ORR: 88%; CR (neg. immunofixation): 12% (n=2); PR 58% (n=10); MR 18% (n= 3); NC 12% (n=2). Median remission duration was 6+ months (range 3–12+ months). Until today, we observed 4 recurrences after 3 – 8 months.

Toxicity comprised mild fatigue and thrombopenia. Lowest platelet count was 55/pL without bleeding, spontaneously reversible within 1 week. Three cases of neuropathia occurred, with controllable symptoms, in patients pretreated with thalidomide or bortezomib mono.

Conclusion: Combination therapy of bortezomib with low dose bendamustine is well tolerated, induces a high rate of responses in spite of unfavourable patient characteristics, leads to early responses and can be limited to 3 months (i.e., 4 cycles), and can be done in an outpatient setting. Thus, bendamustine is a very promising agent to enhance bortezomib action, which warrants further study.