Kumar, Shaji

AbstractExperience with intensive chemotherapy for relapsed/refractory multiple myeloma (RRMM) using VDT PACE regimen and its modifications (VDT PACE‐like regimens: VPLRs) outside TOTAL THERAPY trials is limited. We analyzed the outcomes of 141 patients with RRMM who received VPLRs at our center between 2006 and 2017 in an intent‐to‐treat analysis. Median age was 59.7 years and 66.7% of patients were male. A median of 2.2 years (range 0.02‐11.4) separated diagnosis of myeloma and inititation of VPLR. High‐risk cytogenetics were present in 52.4% patients. Patients received a median of 4 (range 1‐14) prior therapies, including stem cell transplant (SCT) in 66.7% patients. Ninety‐five (67.4%) patients received VDT PACE, 20 (14.2%) patients received VD PACE and 26 (18.4%) patients received other VPLRs. Patients received a median of 1 cycle (range 1‐9) of VPLR. We observed ≥ minimal response in 68.4%, ≥ partial response (PR) in 54.4% and ≥ very good PR in 10.3% patients. Median progression‐free survival was 3.1 months (95% CI, 1.9‐3.9) and median overall survival (OS) was 8.1 months (CI, 6.2‐9.9). One‐hundred and sixteen (82.3%) patients received some therapy after VPLR; 71 (61.2%) received systemic chemotherapy, while 45 (38.8%) underwent SCT. Median OS for those who received SCT after VPLR was 15.1 months (CI, 10.3‐20.8). Age ≥ 60 years (hazard ratio [HR] 2.3 [CI, 1.4‐3.7]; P = 0.0008) and R‐ISS III stage (HR‐ 2.4 [CI, 1.3‐4.0]; P = 0.003) predicted shorter OS in patients receiving VPLR. VPLRs are effective in heavily pre‐treated RRMM. In fit patients, SCT can be used to consolidate the response to VPLR.

AbstractPrimary plasma cell leukemia (pPCL) is the most aggressive form of the plasma cell (PC) malignancy, multiple myeloma (MM). It has been commonly associated with the presence of a chromosome translocation involving the immunoglobulin heavy chain (IgH) locus on 14q32, that is t (11;14). Results from early phase clinical trials utilizing the selective Bcl‐2 inhibitor, venetoclax, as a single agent in patients with relapsed MM have had remarkable efficacy among patients with t (11;14) abnormality. The present case demonstrates the ability of a combination regimen incorporating Bcl‐2 inhibition with daratumumab, bortezomib, venetoclax, and dexamethasone to induce a rapid and very deep hematologic response in a pPCL patient with t (11;14), even in a setting of very refractory disease. This case highlights the need to further study Bcl‐2 inhibition‐based therapy as an option for therapy in patients with pPCL with t (11;14).

Key Points IRd was associated with a consistent PFS benefit vs placebo-Rd in RRMM patients with high-risk and standard-risk cytogenetics. The addition of ixazomib to Rd overcomes the poor PFS associated with high-risk cytogenetics in patients with RRMM.

Key Points Venetoclax monotherapy at a daily dose up to 1200 mg has an acceptable safety profile in patients with relapsed/refractory MM. Venetoclax monotherapy has demonstrated antimyeloma activity in patients with relapsed/refractory MM positive for t(11;14).

AbstractAchievement of a normal FLC ratio (FLCr) following treatment indicates hematologic response and suggests better outcomes in light chain amyloidosis (AL). We examined if elevated involved free light chain (hiFLC) impacts outcomes in patients achieving normal FLCr. We retrospectively analyzed 345 AL patients who were diagnosed within a 10‐year period (2006‐2015) and had 2 consecutive normal FLCr values after 1st line treatment. Among these, patients with hiFLC at 1st reading of normal FLCr (hiFLC1; n = 166; 48.1%) were compared to those who did not (n = 179; 51.9%). Patients with AL who have hiFLC1 after initial therapy had higher rates of multi‐organ involvement (63.3 vs 46.4%; P = .002) and patients in advanced Mayo stage (42.9 vs 32.2%; P = .04) at diagnosis. The median progression free survival [PFS; 38.2 (95%CI; 26.4, 55.4) vs 67.1 (95%CI; 55.8, 88) months; P = .0002] and overall survival [OS; 94.4 (95%CI; 78, 107.1) vs not reached (NR, 95%CI; 116.1, NR) months; P < .0001] were lower in those who had hiFLC1. A more stringent comparison for patients with 2 consecutive hiFLC (hIFLC2; n = 111; 32.2%) versus not (n = 2234; 67.8%) showed consistent results [PFS; 27.1 (95%CI; 23, 53.8) vs 63.3 (95%CI; 55.4, 77) months; P < .0001 and OS; 78 (95% CI; 54.6, 98.8) vs NR (95%CI; NR, NR); P < .0001]. This poor prognostic impact of hiFLC on survival was independent of serum creatinine, Mayo stage, negative immunofixation status and inclusion of transplant in initial therapy on multivariate analysis. Hence, persistent elevation of iFLC predicts poor prognosis even among patients achieving normal ratio after initial therapy in AL.

Key Points In relapsed/refractory MM, venetoclax plus bortezomib and dexamethasone appears to be safe and efficacious. This is a novel therapeutic approach for MM.

Key Points Organ progression at second-line therapy predicated inferior survival. Patients relapsing from >VGPR had a longer time to develop organ progression.