ATLANTA — Pomalidomide (POM) plus low-dose dexamethasone (LoDex) shows promise as a treatment for relapsed and refractory multiple myeloma (RRMM), according to an analysis of data from a phase 2 safety and efficacy trial presented during the 54th American Society of Hematology Annual Meeting and Exposition.
The regimen “is clinically effective and generally well tolerated in patients with RRMM who have received multiple prior treatments including lenalidomide and bortezomib,” reported Sundar Jagannath, MD, of Mount Sinai Medical Center in New York, NY, and colleagues. “POM + LoDex represents an important potential new treatment option for patients with advanced multiple myeloma and appears active in both younger and older patients, with tolerability similar across different age groups.”
Despite advances in multiple myeloma treatment, RRMM remains a serious challenge.
“New anti-myeloma treatments that re-establish tumor response are required to improve survival for patients with advanced, treatment-refractory multiple myeloma,” Dr. Jagannath said.
Patients with at least two prior therapies including lenalidomide and bortezomib followed by disease progression within 60 days of their last treatment were put on a daily low-dose aspirin regimen as a mandatory thromboprophylaxis and randomized 1:1 to receive either POM alone or POM+LoDex (POM, 4 mg/day for Days 1-21 of a 28-day cycle; LoDex, 40 mg/week), the authors reported. Elderly patients (over age 75 years) were administered LoDex at 20 mg/week. (At progression, POM-only-arm patients were allowed to crossover to POM+LoDex.)
Analysis included data from 113 patients in the POM+LoDex arm, for whom mean age was 64 years (range, 34-88) and 88% were younger than 75 years. There were 21 (19%) patients in the POM+LoDex arm who died during the study, due to progressive multiple myeloma (52%), infection, intracranial hemorrhage, acute respiratory distress syndrome, and in one case, a suicide by a severely depressed patient.
Median progression-free survival and overall survival were 4.6 months and 16.5 months, respectively, in the POM+LoDex group overall, the authors reported. In the age subgroup analysis of patients treated with POM+LoDex, the median PFS was 4.7 months in patients ≤65 years, and 3.7 months in patients >65 years. Median OS was 19.7 months in patients ≤65 years and 11.8 months in patients >65 years.
The rate of discontinuations due to adverse events was low (10%). Grade 3 and 4 adverse events occurring in >5% of participants included neutropenia (41%), anemia (22%), pneumonia (22%), thrombocytopenia (19%), fatigue (14%), dyspnea (13%), leukopenia (10%), back pain (10%) and urinary tract infection (UTI, 9%), the authors noted. Deep-vein thrombosis occurred in two patients (2%) and grade 1 or 2 peripheral neuropathy occurred in 7% of patients treated with POM+LoDex.
“Overall, 78% of patients who developed Grade 3 or 4 neutropenia used G-CSF during study treatment,” Dr. Jagannath said. “Grade 3 or 4 neutropenia occurred in 46% of patients aged ≤65 years and in 35% of patients aged >65 years. Despite this, only one patient in each group developed febrile neutropenia (2%).”
In conclusion, “POM was effective in heavily pretreated patients who had already received lenalidomide and bortezomib and who progressed on their last line of therapy. The combination of POM with LoDEX improves the ORR due to synergy between immunomodulatory agents glucocorticoids,” said Dr. Jagannath.
In addition, response was durable with POM regardless of the addition of LoDEX (POM + LoDEX, 8.3 months; POM alone, 8.8 months). Age did not impact ORR, DoR, or safety.
Phase 3 studies of POM+LoDex in combination with bortezomib and other agents are ongoing, the authors reported.