Treatment of Lenalidomide refractory (Len-R) Multiple Myeloma (MM) patients still represents an unmet medical need. Up to now, only the OPTIMISMM study evaluating the efficacy of Pomalidomide-Borte- zomib-Dexamethasone (PVD) recruited a high percentage of Len-R pa- tients, however this combination was only recently approved. Consequently, in the last years Daratumumab-Bortezomib-Dexametha- sone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial In this context, the aim of this real-life study was to evaluate the ef- ficacy and the safety of D-VD in Lenalidomide exposed or refractory patients The study cohort included 57 patients (median age 69 years) af- fected by relapsed/refractory MM. All patients were previously exposed to Lenalidomide, with 77.2% being refractory. Moreover, 89% of cases received ad least a proteasome inhibitor (PI), 17.5% of them being PI refractory. Median line of previous therapy was 2 (1-6), with 22/57 (39%) having received ≥2 lines of therapy. FISH analysis at relapse was available in 30/57 (52.6%) cases and high-risk FISH according to R-ISS was detected in 33.3% of patients. Responses were assessable in 54/57 patients, with overall response rate (ORR) of 79.6% and 43% of cases obtaining at least a Very Good Partial Response (VGPR). D-VD regimen showed a favorable safety profile, with low frequency of grade 3-4 ad- verse events, except for thrombocytopenia in 21.4% of patients. With a median follow up of 13 months, median progression free survival (PFS) and overall survival (OS) were 17 months and not reached, respectively. Patients achieving at least a VGPR showed improved PFS and OS as compared to patients who did not (p=0.0005 and p=0.0443, respectively). No significant PFS differences were found according to previous lines of therapies (≤2 or >2, 20vs15 months, p=0.2682) or to high-risk FISH (16vs20 months, p=0.5432). Len R patients displayed reduced median PFS (16 months) as compared to no Len-R patients (29 months), al- though not statistically significant (p=0.2876). In conclusion, D-VD rep- resents a reliable therapeutic option in previously Lenalidomide treated patients, with high ORR and VGPR rates and favorable safety profile. Finally, even though a higher validation cohort is required, the benefit of this regimen in Len-R patients in real life is remarkable, placing D- VD as one of the standard of care in this setting.
A REAL-LIFE STUDY OF DARATUMUMAB-BORTEZOMIB-DEX- AMETHASONE (DVD) IN LENALIDOMIDE EXPOSED/REFRAC- TORY MULTIPLE MYELOMA PATIENTS: A REPORT FROM THE MYELOMA TRIVENETO WORKING GROUP
F. M. Quaglia;M. Krampera;
2021-01-01
Abstract
Treatment of Lenalidomide refractory (Len-R) Multiple Myeloma (MM) patients still represents an unmet medical need. Up to now, only the OPTIMISMM study evaluating the efficacy of Pomalidomide-Borte- zomib-Dexamethasone (PVD) recruited a high percentage of Len-R pa- tients, however this combination was only recently approved. Consequently, in the last years Daratumumab-Bortezomib-Dexametha- sone (D-VD) combination was extensively used in this setting, even though only a small fraction of Len-R patients was included in the pivotal trial In this context, the aim of this real-life study was to evaluate the ef- ficacy and the safety of D-VD in Lenalidomide exposed or refractory patients The study cohort included 57 patients (median age 69 years) af- fected by relapsed/refractory MM. All patients were previously exposed to Lenalidomide, with 77.2% being refractory. Moreover, 89% of cases received ad least a proteasome inhibitor (PI), 17.5% of them being PI refractory. Median line of previous therapy was 2 (1-6), with 22/57 (39%) having received ≥2 lines of therapy. FISH analysis at relapse was available in 30/57 (52.6%) cases and high-risk FISH according to R-ISS was detected in 33.3% of patients. Responses were assessable in 54/57 patients, with overall response rate (ORR) of 79.6% and 43% of cases obtaining at least a Very Good Partial Response (VGPR). D-VD regimen showed a favorable safety profile, with low frequency of grade 3-4 ad- verse events, except for thrombocytopenia in 21.4% of patients. With a median follow up of 13 months, median progression free survival (PFS) and overall survival (OS) were 17 months and not reached, respectively. Patients achieving at least a VGPR showed improved PFS and OS as compared to patients who did not (p=0.0005 and p=0.0443, respectively). No significant PFS differences were found according to previous lines of therapies (≤2 or >2, 20vs15 months, p=0.2682) or to high-risk FISH (16vs20 months, p=0.5432). Len R patients displayed reduced median PFS (16 months) as compared to no Len-R patients (29 months), al- though not statistically significant (p=0.2876). In conclusion, D-VD rep- resents a reliable therapeutic option in previously Lenalidomide treated patients, with high ORR and VGPR rates and favorable safety profile. Finally, even though a higher validation cohort is required, the benefit of this regimen in Len-R patients in real life is remarkable, placing D- VD as one of the standard of care in this setting.
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