Background. Triplet-based lenalidomide plus dexamethasone combinations have become the new standard of care for early RRMM, including with carfilzomib (KRd). In Aspire phase 3 trial for registration, carfilzomib was given on a dose dense twice a week but not dose intense 20/27 mg/m² dose concentration. In parallel, several studies seem to demonstrate that dose intensity, with increased dose concentration of carfilzomib, could compensate for a less dose dense regimen with carfilzomib weekly. We hypothesized that weekly carfilzomib regimen of KRd will improve time on treatment and quality of life and thus PFS and possibly OS. We aimed to evaluate the efficacy and toxicity of carfilzomib weekly plus lenalidomide/dexamethasone regimen in early RRMM.

Methods. 28 patients were prospectively recruited. Carfilzomib was administered as a 30-minute infusion on days 1,8,15 (at 20mg/m2 on day 1 of cycle 1; then 56mg/m2 thereafter). Lenalidomide (25mg/days) was given 21/28. Dexamethasone was administered weekly.

Results. With a median follow-up of 25 months, 42% relapsed and 17% died. Importantly, 16/28 (57%) are still on treatment. The median number of cycles was 18, with 32% of patients treated more than 20 cycles. Only 4 patients stopped weekly KRd for safety issues. ORR and CBR was 85.7% and 89.3%, whom 43% ≥CR; with a median DOR of 13 months and 43% having more than 18 months. 7 patients had negative MRD at 10-5 and normalized PET CT. The projected PFS, EFS and OS at 30 months were 56%, 43% and 82%, respectively. Hematologic and non-hematologic adverse events ≥ grade 3 were reported in 57% and 36%, respectively. Adverse events ≥ grade 3 seen in ≥10% of patients were neutropenia, thrombocytopenia, vomiting and pyrexia.

Conclusion. KRd weekly at 20/56mg/m2 is effective and safe to early RRMM patients, provides improved safety profile and QOL to patients allowing treating patients until progression. Further studies are warranted to confirm this data on a larger early RRMM population and validate the ability to use dose intensity to improve the dose density approach using carfilzomib combination.

Disclosures

Leleu:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

Topics:
carfilzomib, dexamethasone, lenalidomide, multiple myeloma, adverse event, computed tomography/positron emission tomography imaging, dose-dense chemotherapy, fever, follow-up, infusion procedures

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2018 by The American Society of Hematology
2018
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