Adding Lenalidomide to Melphalan/Prednisone Yields Better Quality of Life Than Thalidomide in Elderly Patients With Multiple Myeloma
A phase III Eastern Cooperative Oncology Group (ECOG) trial (E1A060) comparing melphalan, prednisone, and thalidomide (Thalomid) (MPT-T) with melphalan, prednisone, and lenalidomide (Revlimid) (mPR-R) in elderly patients with untreated multiple myeloma found that at the end of the induction period, patients receiving the lenalidomide combination had “a statistically superior” quality of life.
There were no statistical or clinically relevant differences in response rates, progression-free survival, or overall survival.
“Much of this difference [in quality of life] appears attributable to lower neuropathy rates with lenalidomide than with thalidomide,” Stewart et al reported in Blood.
A total of 306 patients enrolled, 154 in the MPT-T arm and 152 in the mPR-R arm. “Seven cooperative groups contributed, with 66% of patients coming from 33 participating ECOG centers,” the researchers noted.
Eligible patients had a confirmed diagnosis of multiple myeloma with evidence of end-organ damage at the time of diagnosis, and were either 65 years of age or older and had declined alternative treatment or were under 65 years and were not candidates for or had declined autologous stem cell transplantation. The median age of the study participants was 75.7 years. ECOG performance status ≤ 2 was required.
Overall Survival Near 4 Years
As induction therapy, patients received either 9 mg/m2 melphalan and 100 mg prednisone orally on days 1 to 4 with 100 mg thalidomide daily or 5 mg/m2 melphalan and 100 mg prednisone orally on days 1 to 4 with 10 mg lenalidomide orally on days 1 to 21. The authors explained that they used “the designation mPR-R to delineate the lower doses of melphalan that can be coadministered as well as continuous use of lenalidomide, with a hypothesis that mPR-R would be noninferior and possible superior in terms of toxicity and survival outcomes.”
Patients continued on therapy for 12 28-day cycles followed by 100 mg thalidomide or 10 mg lenalidomide daily until progression or unacceptable toxicity. “Mean duration of overall treatment (induction and maintenance) was 15.6 months on MPT-T and 14.9 months on mPR-R for the entire study cohort,” the authors noted.
The median follow-up was 40.7 months. For the primary intention-to-treat analysis, the median progression-free survival observed was 21.0 months for patients receiving MPT-T vs 18.7 months for those receiving mPR-R (hazard ratio [HR] = 0.84, 95% confidence interval [CI] = 0.64–1.09, P = .186). Overall survival was 52.6 months with MPT-T vs 47.7 months with mPR-R (HR = 0.88, 95% CI = 0.63–1.24, P = .476). “Per-protocol response rates were 63.6% (MPT-T) and 59.9% (mPR-R) (P = .557),” the investigators reported.
‘Both Regimens Proved Toxic’
“Both regimens proved toxic,” the authors wrote. “At least 58% of mPR-R patients and 73% of MPT-T patients experienced grade 3 toxicity, and half the patients discontinued treatment before finishing 12 months of planned induction therapy, with toxicity being the primary reason (42%) for stopping treatment.”
Patients receiving MPT-T had significantly higher ≥ grade 3 nonhematologic toxicity, 59.5% vs 40.0% receiving mPR-R (P = .001). “There was also a notable age effect in the MPT-T arm, “ the investigators noted, with 47.2% of those > 75 years experiencing a grade ≥ 3 adverse event vs 35.6% of patients < 75 years. “This difference in tolerability by age was not significant in mPR-R patients,” the authors wrote.
Grade ≥ 3 events occurring in > 5% of patients included anemia, leukopenia, lymphopenia, neutropenia, fatigue, platelets, constipation, and dyspnea (in the MPT-T arm only). Deep vein thrombosis or pulmonary embolism was observed in 8.8% of the MPT-T and 6.7% of the mPR-R patients. Second malignancies occurred in 18 MPT-T patients and 14 mPR-R patients.
A. Keith Stewart, MBChB, of Mayo Clinic Arizona in Scottsdale, is the corresponding author for the Blood article.
For full disclosures of the study authors, visit www.bloodjournal.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
