Improved survival of patients with primary plasma cell leukemia with VRd or daratumumab‐based quadruplets: A multicenter study by the Greek myeloma study group

Abstract

We evaluated the efficacy and prognostic impact of bortezomib‐lenalidomide triplet (VRd) or daratumumab‐based quadruplets (DBQ) versus previous anti‐myeloma therapies, that is, bortezomib standard combinations (BSC) or conventional chemotherapy (CT), in a large cohort of patients with primary plasma cell leukemia (pPCL), including those fulfilling the revised diagnostic criteria, that is, circulating plasma cells (cPCS): ≥5%; 110 pPCL patients (M/F: 51/59; median age 65 years, range: 44–86) out of 3324 myeloma patients (3%), registered in our database between 2001 and 2021, were studied; 37% had cPCS 5%–19%; 89% received novel combinations including DBQ (21%), VRd (16%) and BSC (52%); 35% underwent autologous stem cell transplantation. 83% achieved objective responses. Treatment with VRd/DBQ strongly correlated with a higher complete response rate (41% vs. 17%; p = .008). After a median follow‐up of 51 months (95% CI: 45–56), 67 patients died. Early mortality was 3.5%. Progression‐free survival was 16 months (95% CI: 12–19.8), significantly longer in patients treated with VRd/DBQ versus BSC/CT (25 months, 95% CI: 13.5–36.5 vs. 13 months 95% CI: 9–16.8; p = .03). Median overall survival (OS) was 29 months (95% CI: 19.6–38.3), significantly longer in patients treated with VRd/DBQ versus BSC/CT (not reached vs. 20 months, 95% CI: 14–26; 3‐year OS: 70% vs. 32%, respectively; p < .001; HzR: 3.88). In the multivariate analysis VRd/DBQ therapy, del17p(+) and PLT <100.000/μL, independently predicted OS (p < .05). Our study has demonstrated that in the real‐world setting, treatment with VRd/DBQ induces deep and durable responses and is a strong prognostic factor for OS representing currently the best therapeutic option for pPCL.

A Clinical Perspective on Plasma Cell Leukemia: A Single-Center Experience

“…A retrospective multicenter study by the Greek Myeloma Study Group investigated patients with pPCL defined as ≥5% CPCs. They reported that patients who received VRd (bortezomib-lenalidomide-dexamethasone) or daratumumab-based quadruplets had a higher complete response (CR) rate of 41%, with an improved median PFS of 25 months and a median OS not reached in comparison to conventional chemotherapy or best supportive care [ 30 ]. Other groups reported conflicting data regarding the magnitude of the improved outcomes with aggressive regimens, including allogeneic transplantation [ 18 , 31 , 32 ].…”

Treatment of primary plasma cell leukaemia with carfilzomib and lenalidomide-based therapy (EMN12/HOVON-129): final analysis of a non-randomised, multicentre, phase 2 study

“…10 New agents with novel mechanisms of action should also be investigated in this disease. Daratumumab-containing regimens are increasingly used to treat patients with newly diagnosed primary plasma cell leukaemia, based on promising results from retrospective studies, 23 as well as favourable clinical outcomes in multiple myeloma. 24,25 Ongoing clinical trials (such as NCT0587091 and NCT05219721) are evaluating whether incorporation of T-cell redirecting therapies (eg, CAR T-cell therapy and bispecific antibodies) in the treatment strategy further improves depth of response and survival of patients newly diagnosed with primary plasma cell leukaemia.…”

Primary plasma cell leukaemia presenting as unilateral proptosis

“…Although the prognosis of patients with pPCL has significantly improved with daratumumab-based quadruplets, del17p(+) predicts poor outcome [2].…”