AN INTERNATIONAL, MULTICENTER, PROSPECTIVE, OBSERVATIONAL STUDY OF NEUTROPENIA IN PATIENTS BEING TREATED WITH LENALIDOMIDE + DEXAMETHASONE FOR RELAPSED OR RELAPSED/REFRACTORY MULTIPLE MYELOMA (RR-MM)

ABSSUB-4862

Background: Neutropenia is a common dose-limiting toxicity in patients with multiple myeloma receiving lenalidomide regimens. At the present time, little information is available regarding the characterization of neutropenia events and their optimal management in this setting.

Aims: This prospective observational study was designed to characterize neutropenia, its management, and its impact on delivery of lenalidomide regimens in patients with RR-MM in a clinical practice setting.

Methods: Eligible patients were ≥ age 18, had been diagnosed with relapsed or relapsed and refractory MM, and provided informed consent where required by local regulations. Patients were either starting treatment with lenalidomide plus dexamethasone or were still in their first cycle at the time of enrollment. Patients were observed from the start of lenalidomide treatment for up to 12 months. Data collected at each routine office visit included: lenalidomide administration, including any dose interruptions or reductions; absolute neutrophil count and body temperature if noted; G-CSF use; and hospitalizations related to MM. The primary outcome was the incidence of grade 3/4 neutropenia.

Results: A total of 198 eligible patients were enrolled between February 2011 and July 2012 at 34 centers in 9 countries (Australia, Austria, Czech Republic, France, Germany, Greece, Ireland, Spain, and UK). All patients were included in the primary analysis set and 69 (35%) completed the 12-month observational period. The most common reasons for early withdrawal were disease progression (21%), tolerability issues with lenalidomide (15%), and death (12%). Fifty-four percent of patients were men and the median age was 70. Most patients (83%) had a current diagnosis of relapsed MM, and the median time from the initial to current diagnosis was 36 months. At baseline, 21% of patients were stage III per the International Staging System. Most (60%) had 1-2 prior therapies and comorbidities were present in 84% of patients. Most patients (68%) received 25 mg/d lenalidomide in the standard schedule (days 1-21), 61% of patients received the dexamethasone dose and schedule included in the lenalidomide prescribing information. For the primary outcome, 62 patients (31%; 95% CI: 25 - 38%) had at least one grade 3/4 neutropenia event and the median time to first grade 3/4 neutropenia was 8.8 weeks (Q1, Q3: 5.9 – 17.3 weeks); half the patients with grade 3/4 neutropenia had 3 or more events. Six patients (3%) experienced febrile neutropenia. G-CSF was used in 23% of patients; filgrastim was administered for a mean of 6.9 days and a median of 1.0 day (range: 1-141). More patients with than without grade 3/4 neutropenia experienced lenalidomide dose reduction (37% vs 18%), received G-CSF (40% vs 15%), and experienced unplanned hospitalizations (50% vs 42%).

Summary/Conclusion: Incidence of grade 3/4 neutropenia in patients with RR-MM receiving lenalidomide and dexamethasone in clinical practice was similar to that reported in phase 3 studies. Grade 3/4 neutropenia events occurred in later cycles than the cytotoxic chemotherapy setting; therefore, different neutropenia monitoring and management may be required. G-CSF use was reactive rather than prophylactic. While lenalidomide toxicity is usually first managed with dose modifications per consensus panel guidelines (Dimopoulos et al, 2011), G-CSF support may be important for patients to maintain optimal dosing for continued response.

Keywords: Immunomodulatory thalidomide analog, Multiple myeloma, Myelosuppression, Neutropenia

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