MADRID—New research suggests one triplet regimen may be more active but also more toxic than another in patients with newly diagnosed multiple myeloma (MM).
In the FORTE trial, the combination of carfilzomib, lenalidomide, and dexamethasone (KRD) produced higher response rates than carfilzomib, cyclophosphamide, and dexamethasone (KCD).
However, treatment with KRD also produced significantly more grade 3/4 non-hematologic adverse events (AEs) and serious AEs than the KCD regimen.
Francesca Gay, MD, PhD, of University of Torino in Italy, presented these results, from a planned interim analysis of FORTE, at the 22nd Congress of the European Hematology Association (EHA) as abstract S410.
The trial enrolled 477 MM patients younger than 65 years of age.
The patients were randomized to receive:
- Four 28-day KCD cycles (n=154)
Carfilzomib at 20 mg/m2 (for cycles 1 and 2) or 36 mg/m2 (for subsequent cycles) on days 1, 2, 8, 9, 15, and 16
Cyclophosphamide at 300 mg/m2 on days 1, 8, and 15
Dexamethasone at 20 mg on days 1, 2, 8, 9, 15, 16, 22, and 23
- Four 28-day KRD cycles (n=309)
Carfilzomib and dexamethasone as above
Lenalidomide at 25 mg on days 1-21
After the fourth induction cycle, all patients received cyclophosphamide at 2 g/m2, followed by peripheral blood stem cell (PBSC) collection for autologous stem cell transplant.
The median age was 57 (range, 52-62) in the KCD arm and the KRD arm (range, 51-62). In both arms, 55% of patients were male.
Roughly half of patients in both arms had an ISS stage of I (52% in the KCD arm and 51% in the KRD arm), 31% of patients in both arms were stage II, and 17% were stage III.
Fifty-eight percent of patients in the KCD arm and 59% in the KRD arm did not have t(4;14), t(14;16), or del17. Thirty-one percent and 26%, respectively, did have one of these cytogenetic abnormalities. (For the remaining patients, cytogenetic risk data were missing.)
PBSC mobilization and response
The median number of PBSCs collected was 8.6 x 106/kg in the KCD arm and 6.3 x 106/kg in the KRD arm. Plerixafor was required in 6% of patients in the KCD arm and 28% of patients in the KRD arm (P<0.001).
Ninety-two percent of patients in the KCD arm and 96% in the KRD arm had a partial response or better. Sixty-one percent and 74%, respectively, had a very good partial response (P=0.01). Six percent and 15%, respectively, had a complete response.
Grade 3/4 hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) were thrombocytopenia (2% and 1%), neutropenia (6% and 5%), and anemia (2% and 3%). Seven percent of KRD patients and 6% of KCD patients had at least 1 grade 3/4 or serious hematologic AE.
Grade 3/4 non-hematologic AEs and serious AEs (in the KRD and KCD arms, respectively) included dermatologic events (8% and 1%, P<0.001), renal events (1% and 2%), fever (4% and 1%), infections (5% and 3%), gastrointestinal AEs (2% and 1%), hepatic events (8% and 1%, P<0.001), venous thromboembolism (1% and 0%), hypertension (3% and 2%), and cardiac events (1% and 2%).
Thirty-two percent of KRD patients and 16% of KCD patients had at least 1 grade 3/4 or serious non-hematologic AE (P<0.001).
Four percent of patients in the KRD arm and 2% in the KCD arm discontinued treatment due to AEs. Fifteen percent and 6%, respectively, reduced the dose of at least 1 drug (P=0.005).
One percent of patients in the KRD arm and 2% in the KCD arm died from AEs. In the KCD arm, 1 patient had a sudden death, and 1 died of pneumonia. In the KRD arm, there was 1 sudden death in a patient with sepsis, 1 patient died of infection, and 1 died of cardiac arrest (this patient previously discontinued treatment due to renal failure).