Relapsed/Refractory Multiple Myeloma Patients Treated with Lenalidomide/Dexamethasone Who Achieve a Complete or near Complete Response Have Longer Overall Survival and Time to Progression Compared with Patients Achieving a Partial Response.

Background: There is ongoing debate about what would be considered an acceptable response to therapy in patients with relapsed/refractory multiple myeloma (MM). Lenalidomide (Len) is an immunomodulatory compound. Two recent phase III randomised trials (MM-009 and MM-010) showed Len in combination with Dexamethasone (Dex) provided significantly better overall response (OR), complete response (CR), overall survival (OS) and time to progression (TTP) compared with Dex alone in patients with relapsed/refractory MM. Approximately 60% of patients achieved an OR (61% in MM-009 and 60% in MM-010), including a CR in 15% (14% and 16%, respectively), Median OS was ≥29.5 months (29.5 and not yet reached) and median TTP was ≥11.1 months (11.1 months and 11.3 months, respectively). Here, we compare outcomes in patients with a CR or near CR (nCR) vs those with a partial response (PR).

Methods: Data for patients who received Len/Dex in the MM-009 or MM-010 studies were pooled for this analysis. Patients received Len (25 mg/day on days 1–21 of every 28-day cycle) and Dex 40mg PO q.d. on days 1–4, 9–12, and 17–20 (for the first four cycles). After 4 cycles, Dex 40 mg/day was administered only on days 1–4. Response to therapy, TTP, OS, duration of response, and time to response, as well as adverse events were assessed. Response rate and TTP are based on data obtained before unblinding (June 2005 [MM-009] and August 2005 [MM-010]).

Results: Of 353 patients treated with Len/Dex, 214 (61%) had PR or better (86 with CR/nCR; 128 with PR). Baseline characteristics were comparable between patient groups; most patients had stage III disease (63% vs 66%) and an Eastern Cooperative Oncology Group (ECOG) score of 0–1 (83% vs 90%). More patients with CR/nCR had received ≥2 prior antimyeloma regimens/stem cell transplant than patients with PR (88% vs 70%). Patients with CR/nCR had significantly longer median TTP and OS compared with those with PR (Table). The median duration of response was significantly higher among patients with CR/nCR (not yet reached vs 38 weeks; p<0.001). Fewer patients with CR/nCR relapsed compared with those with PR (38% vs 43%). The times to CR/nCR and PR were comparable. The most common grade 3–4 adverse events were neutropenia (43% vs 41%), thrombocytopenia (13% vs 16%), anaemia (12% vs 9%) and pneumonia (12% vs 6%). Rates of febrile neutropenia were low (1% vs 3%).

Conclusion: Len/Dex treatment is associated with longer OS and TTP in patients with relapsed/refractory MM who achieve a CR than in patients who achieve a PR.