Abstract
Introduction: Plasma cell leukemia (PCL) is an aggressive variant of multiple myeloma (MM) characterized by circulating plasma cells in the peripheral blood. It can occur as a de novo presentation, termed primary PCL (pPCL), or as a leukemic transformation of MM, termed secondary PCL (sPCL). Despite advances in MM therapies, outcomes for both pPCL and sPCL remain poor. Due to its rarity, heterogeneity, and exclusion from most clinical trials, treatment strategies for PCL are inconsistent and largely informed by limited studies and extrapolation from MM data. Here, we present a retrospective review of all patients with PCL treated at Northwell Health.
Methods: We performed a retrospective chart review of patients diagnosed and treated for pPCL and sPCL between January 1, 2016 and December 31, 2024, at Northwell Health. PCL was defined as > 5% circulating plasma cells based on the International Myeloma Working Group (IMWG) consensus definition. Patient baseline characteristics, presentation, treatment regimens, response, and survival outcomes were recorded. Progression free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier curves.
Results: This cohort included 18 patients with pPCL and 5 with sPCL, with a median age at diagnosis of 59 years (range 35–90). The majority were female (n=14, 60%) and Black (n=9, 40%), with an increased prevalence of high-risk cytogenetics (n=14, 60%) and complex karyotypes (n=17, 74%). Common abnormalities included t(4;14) (n=7, 30%), RB1 deletion (n=16, 70%), t(11;14) (n=6, 26%), and del(17p) (n=8, 35%). Anemia was the most frequent presenting feature (n=18, 78%), followed by hypercalcemia, renal failure, and lytic lesions, each observed in 10 patients (43%).
Induction regimens included conventional chemotherapy (n=8, 35%), quadruplet therapies (n=8, 35%), and triplet therapies (n=7, 30%). The most common regimens were VD-PACE (n=4) among conventional chemotherapy, Dara-CyBorD (n=4) among quadruplets, and CyBorD (n=4) among triplets. Amongst the group of patients who received Dara-CyBorD, 2 had significant renal insufficiency and all four were admitted at initial diagnosis of PCL limiting access to other therapies at diagnosis. The rate of autologous stem cell transplant (ASCT) was surprisingly low, with only 7 patients (30%) completing ASCT during first line therapy. In the group of patients that did not receive first-line ASCT, 3 had rapid progression of disease while on first line therapy and 3 had poor performance status. For salvage therapies, 4 patients received DCEP, 2 received PACE-based regimens, 1 patient achieved remission while on teclistamab, one had delayed ASCT (with third line therapy), and one received CAR-T therapy.
PFS on first-line therapy (PFS1) was 124 days (95% CI: 58–261) for the entire cohort, 129 days (95% CI: 35–371) for pPCL, and 103 days (95% CI: 8– Not reached (NR)) for sPCL. OS was 494 days (95% CI: 230–1165) for all patients, 509 days (95% CI: 350–NR) for pPCL, and 156 days (95% CI: 94–NR) for sPCL. Median PFS1 for patients receiving chemotherapy, quadruplet, and triplet induction was 113.5, 129.5, and 58 days, respectively. The corresponding OS was 484, 230, and 509 days. There was no statistically significant difference in PFS1 (p = 0.86) or OS (p = 0.57) between patients who received conventional chemotherapy and those treated with a daratumumab-based quadruplet induction regimen. Of note, the majority of patients that received these quadruplet regimens did not receive lenalidomide or carfilzomib for induction of PCL.
Conclusions: Although the results of this retrospective study showed that there was no significant difference in PFS1 and OS based on induction regimens, some patients received suboptimal regimens due to various constraints including prior treatment regimens, comorbidities, socioeconomic factors, and variabilities in access to care. Despite therapeutic advances in MM, PFS and OS in patients with both pPCL and sPCL remains poor, underscoring the need for further prospective trials to determine optimal treatment patterns and sequencing.
