In a European phase II trial (EMN12/HOVON-129) reported in The Lancet Oncology, van de Donk et al found that the incorporation of carfilzomib and lenalidomide into induction, consolidation, and maintenance therapies was associated with good outcomes in both younger and older patients with primary plasma cell leukemia.
Study Details
Sixty-one patients were enrolled in the trial from sites in Belgium, Czech Republic, Denmark, Italy, Norway, Netherlands, and the United Kingdom between October 2015 and August 2021; of these patients, 36 were aged 18 to 65 years and 25 were aged ≥ 66 years.
Younger patients received four 28-day cycles of carfilzomib/lenalidomide/dexamethasone (KRd) induction, with carfilzomib at 36 mg/m² on days 1, 2, 8, 9, 15, and 16; lenalidomide at 25 mg on days 1 to 21; and dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23. KRd induction was followed by double autologous hematopoietic stem cell transplantation (HSCT); four cycles of KRd consolidation; and maintenance therapy with carfilzomib at 27 mg/m² on days 1, 2, 15, and 16 for the first twelve 28-day cycles and 56 mg/m² on days 1 and 15 in all subsequent cycles; and lenalidomide at 10 mg on days 1 to 21. Patients eligible for allogeneic HSCT could also receive a single autologous HSCT followed by reduced-intensity conditioning allogeneic HSCT and then carfilzomib/lenalidomide maintenance.
Older patients received eight cycles of KRd induction followed by carfilzomib/lenalidomide maintenance.
In both groups, treatment was continued until disease progression.
The primary endpoint was progression-free survival in the intention-to-treat population. Based on historical treatment data in primary plasma cell leukemia, median progression-free survival was approximately 9 months among younger patients and 6.5 months among older patients.
Progression-Free Survival Outcomes
Median follow-up among younger patients was 43.5 months (interquartile range = 27.7–67.8 months). Median progression-free survival among younger patients was 15.5 months (95% confidence interval [CI] = 9.4–38.4 months). For older patients, median follow-up was 32.0 months (IQR = 24.7–34.6 months). Median progression-free survival was 13.8 months (95% CI = 9.2–35.5 months).
KEY POINTS
- Median progression-free survival was 15.5 months among younger patients and 13.8 months among older patients.
- Partial response or better was achieved in 86% and 80%, and complete response or better was achieved in 50% and 36%.
Throughout treatment, best response of partial response or better was achieved in 86% of younger patients and 80% of older patients, very good partial response or better was achieved in 83% and 68%, and complete response or better was achieved in 50% and 36%.
Median overall survival was 28.4 months (95% CI = 15.1 months to not evaluable) among younger patients, with an early mortality rate of 8.3% at 6 months. Median overall survival was 24.8 months (95% CI = 14.0 months to not evaluable) among older patients, with an early mortality rate of 16% at 6 months.
Adverse Events
During the first four KRd cycles, grade ≥ 3 hematologic and nonhematologic toxicity occurred in 8% and 44% of patients in the younger group; the most common nonhematologic events were cardiac, gastrointestinal, respiratory, vascular, renal, and infectious (occurring in 6% of patients each). In the older group, grade ≥ 3 hematologic and nonhematologic toxicity occurred in 16% and 64%. The most common nonhematologic events were infectious (32%), respiratory (16%), gastrointestinal (8%), and vascular (8%). Treatment-related serious adverse events occurred in 72% of the younger group and 76% of the older group, mainly infection in both groups. Treatment-related deaths occurred in none of the younger patients and in three (12%) of the older patients (due to infection in two and unknown cause in one).
The investigators concluded, “Carfilzomib and lenalidomide–based therapy provides improved progression-free survival compared with previously published data. However, results remain inferior in primary plasma cell leukemia compared with multiple myeloma, highlighting the need for new studies incorporating novel immunotherapies.”
Niels W.C.J. van de Donk, MD, PhD, of Amsterdam UMC, Department of Hematology, Vrije Universiteit Amsterdam, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the Dutch Cancer Society, Celgene, and Amgen. For full disclosures of the study authors, visit thelancet.com.
