2017 ASCO Annual Meeting: Carfilzomib frontline in newly diagnosed MM

The Multiple Myeloma Hub was delighted to attend the 2017 ASCO Annual Meeting at McCormick Place in Chicago, Illinois.  The congress was held from June 2^nd to 6^th, with attendance from oncology professionals across the globe.  The MM Hub is pleased to present a summary highlighting the use of carfilzomib frontline therapy in newly diagnosed multiple myeloma (NDMM) patients. 

On Sunday June 4^th, Professor Francesca Gay from the University of Torino in Italy shared an interim analysis of the FORTE study of newly diagnosed myeloma patients. This study compared carfilzomib, lenalidomide and dexamethasone (KRd) to carfilzomib, cyclophosphamide and dexamethasone, for induction therapy in NDMM patients.  The full study includes three treatment arms, two randomized to receive autologous transplant and one arm to receive continued therapy with eight cycles of KRd. The aims of the study were to evaluate safety and efficacy of the induction phase, and measure rate of failure of peripheral stem cell mobilization (PBSC).

• Total of 477 patients (pts) are enrolled and mobilization was evaluable for 333 patients
• Pts ≤65 years old
• Most common hematologic adverse events (AEs): thrombocytopenia, neutropenia, and anemia
• Non-hematologic AEs: dermatologic, renal, fevers/infections, gastro-intestinal, elevated hepatic enzymes and cardiac
• Significantly more grade 3-4 rashes and hepatic enzyme elevations in KRd
• More KRd pts required at least one drug dose reduction (15% vs. 6%, p=0.005)
• Lenalidomide was more frequently reduced than cyclophosphamide (11% vs. 1% p=<0.01)
• All pts were mobilized 4-6 wks after the start of the 4^th cycle with cyclophosphamide and filgrastim
• More patients treated with KRd required plerixafor for PBSC mobilization (28% vs. 6%, p=<0.001)
• A greater percentage of patients treated with KRd achieved ≥VGPR (74% vs.61%, p=0.01)
• In conclusion, KRd shows higher efficacy, but this comes at the cost of increased AEs.

Professor Xavier Leleu from Poitiers University Hospital followed with an excellent presentation about carfilzomib and weekly melphalan-prednisone in untreated, elderly myeloma patients. The aims of the study were to determine the maximum tolerated dose (MTD) of weekly carfilzomib, safety and response to therapy.

• Dosing schedule: carfilzomib 36, 45, 56 and 70 mg/m² on days 1, 8, 15 and 22 in 35-days cycles, with oral Melphalan and Prednisone given on days 1 to 4
• Pts received 9-cycles of induction followed by carfilzomib monotherapy maintenance at 36 mg/m² every 2 weeks for 1 year
• Total of 24 pts were analyzed for initial safety and efficacy of doses escalation
• Grade 3 toxicities = 4 pts
• AEs in 56 mg/m²  cohort: febrile neutropenia (n=1) and cardiac failure (n=1)
• AEs in 70 mg/m²  cohort: grade 3 nausea and vomiting (n=1) and increase in liver GGT (n=1)
• Following initial data, dosing protocol was amended to a maximum carfilzomib dose of 56 mg/m² for pts > 75 years old and 70 mg/m² for pts ≤ 75 years
• Response rates were favorable across all treatment groups
• ORR, ≥VGPR and ≥CR rates were 89.9%, 70% and 46.6% respectively (n = 30)

This study demonstrated that promising responses are possible with carfilzomib weekly maintenance and that dose reduction is important for elderly patients.

In summary, these two presentations provided promising data for the use of carfilzomib in the setting of NDMM patients.