[Analysis of the prognostic factors in primary plasma cell leukemia in the era of novel agents].

Objective: To explore the prognostic factors of primary plasma cell leukemia (pPCL) in the era of novel agents. Methods: The clinical data of 66 patients with pPCL treated at the Department of Haematology, Beijing Chao-Yang Hospital, Capital Medical University from 2011 to 2022 were retrospectively collected to analyze their prognostic factors. Results: Among the 66 patients with pPCL, the median age was 59 (range: 29-79) years. The median overall survival (OS) duration was 19.0 (95% CI 10.4-27.6) months, and the median progression-free survival (PFS) duration was 11.0 (95% CI 6.5-15.6) months. The median OS and PFS were significantly longer in patients with the best post-treatment response of very good partial remission (VGPR) or better than in patients with a response of partial remission (PR) or worse (median OS: 33.0 months vs 6.0 months, P<0.001; median PFS: 16.0 months vs 3.0 months, P<0.001). OS was significantly longer in patients who underwent autologous hematopoietic stem cell transplantation than in those who did not undergo transplantation (49.0 months vs 6.0 months, P=0.002), and there was a trend toward a longer PFS in patients who underwent transplantation than in those who did not undergo transplantation (19.0 months vs 8.0 months, P=0.299). The median OS and PFS were significantly longer in patients who received maintenance therapy than in those who did not receive maintenance therapy (median OS: 56.0 months vs 4.0 months, P<0.001; median PFS: 20.0 months vs 2.0 months, P<0.001). Multivariate analysis showed that hypercalcemia was an independent risk factor (HR=3.204, 95% CI 1.068-9.610, P=0.038) for patients with pPCL, while receiving maintenance therapy (HR=0.075, 95% CI 0.022-0.253, P<0.001) and post-treatment response of VGPR or better (HR=0.175, 95% CI 0.048-0.638, P=0.008) were independent protective factors for patients with pPCL. Conclusions: In the era of novel agents, hypercalcemia, receiving maintenance therapy, and post-treatment response of VGPR or better are independent prognostic factors for pPCL.

Poor outcome despite modern treatments: A retrospective study of 99 patients with primary and secondary plasma cell leukemia.

BACKGROUND: Plasma cell leukemia (PCL) is a rare monoclonal gammopathy, associated with short survival. Because of its very low incidence, only a few cohorts have been reported and thus, information on this disease is scarce. The goal of this study was to better understand the clinical features, prognostic factors, and efficacy of modern treatments in both primary PCL (pPCL) and secondary PCL (sPCL). METHODS: We performed a retrospective, multicenter study of patients diagnosed with PCL, defined as circulating plasma cells ≥20% of total leukocytes and/or ≥2 × 109/L. RESULTS: We identified 99 eligible PCL patients, of whom 33 were pPCL and 66 were sPCL. The median progression-free survival (PFS) to frontline treatment and overall survival (OS) were, respectively, 4.8 (95% CI, 0.4-9.2) and 18.3 months (95% CI, 0.0-39.0) for pPCL and 0.8 (95% CI, 0.5-1.1) and 1.2 months (95% CI, 0.9-1.5) for sPCL (both p < 0.001). We observed no improvement in OS over time (2005-2012 vs. 2013-2020, p = 0.629 for pPCL and p = 0.329 for sPCL). Finally, our data suggested that sPCL originates from a high-risk multiple myeloma (MM) population with a short OS (median 30.2 months), early relapse after stem cell transplant (median 11.9 months) and a high proportion of patients with multiple cytogenetic abnormalities (36% with ≥2 abnormalities). CONCLUSIONS: This study is one of the largest PCL cohorts reported. We are also the first to investigate characteristics of MM before its transformation into sPCL and demonstrate that high-risk biologic features already present at the time of MM diagnosis. Moreover, our data highlights the lack of improvement in PCL survival in recent years and the urgent need for better treatment options.

Development of a clinical prognostic model for primary plasma cell leukemia patients treated with novel agents: a multicenter retrospective cohort study.

The prognosis of primary plasma cell leukemia (pPCL) is poor, and the relevant prognostic factors are incompletely understood. We aimed to explore the prognostic factors and develop a validated prognostic prediction model for pPCL patients in the new era. This multicenter retrospective study was conducted across 16 hospitals in China. Cox proportional hazards regression analysis was used to develop a prediction model. The predictive performance of the model was assessed using multiple metrics. Internal validation was conducted using bootstrap resampling. A total of 102 pPCL patients were included in this study, and 57 (55.9%) were male. The 12-month, 24-month, and 36-month OS rates for pPCL patients were 75.4%, 58.3%, and 47.6%, respectively. An overall survival prognostic nomogram for pPCL patients was established by integrating independent prognostic factors, including age, B2MG, and del17p. The nomogram exhibited good performance, with a C-index of 0.720 (95% CI 0.642-0.797) and an AUC of 0.653. Bootstrap validation yielded a C-index of 0.721 (95% CI 0.629-0.787) and an AUC of 0.653 (95% CI 0.546-0.759), indicating a relatively good fit of the calibration curve. A nomogram incorporating age, B2MG grade, and del17p were developed and validated to accurately and consistently predict the prognosis of pPCL patients.

Plasma Cell Leukemia with Successful Upfront Venetoclax in Combination with Allogeneic Transplantation.

BACKGROUND Plasma cell leukemia (PCL) is an aggressive form of plasma cell neoplasm. We report the first case of primary PCL successfully treated with upfront novel agents consisting of Venetoclax and daratumumab in combination with intensive chemotherapy and allogeneic transplantation. CASE REPORT A 59-year-old woman presented with epistaxis, gum bleeding, and blurred vision. On examination, she appeared pale, with multiple petechiae and hepatomegaly. Fundoscopy revealed retinal hemorrhages. Laboratory investigations revealed bicytopenia and leukocytosis, with mild coagulopathy and hypofibrinogenemia. Elevated globulin and calcium levels were also observed. Serum protein electrophoresis demonstrated IgG lambda paraproteinemia, with a serum-free light chain kappa-to-lambda ratio of 0.074. A skeletal survey revealed the presence of lytic lesions. Bone marrow investigations confirmed the presence of lambda-light-chain-restricted clonal plasma cells. FISH detected t(11;14) and 17p13.1 deletion. Therefore, a final diagnosis of primary PCL was made. The patient received 1 cycle of bortezomib, cyclophosphamide, and dexamethasone (VCD) and 5 cycles of Venetoclax-VCD, followed by an unsuccessful stem cell mobilization. One cycle of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (VRD) was then given. The patient achieved complete remission. She underwent allogeneic stem cell transplantation of an HLA-matched sibling donor. Post-transplant marrow assessment showed disease remission and absence of t(11;14) and 17p deletions. She was administered pamidronate and lenalidomide maintenance. She remained clinically well with a good performance status and no active graft-versus-host disease 18 months after transplant. CONCLUSIONS The success of our patient in achieving complete remission has highlighted the efficacy and safety of this novel therapy in the front-line management of PCL.

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

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.

Isolated relapse of plasma cell leukemia in the central nervous systems: a case report and literature review.

Plasma cell leukemia is a rare yet aggressive form of multiple myeloma characterized by high levels of plasma cells circulating in the peripheral blood. We recently experienced a case of plasma cell leukemia that had been in stringent complete remission for nine years after autologous stem cell transplantations with subsequent courses of lenalidomide maintenance therapy, and then relapsed as an extramedullary plasmacytoma in the central nervous system. Assessment of the bone marrow did not prove proliferation of plasma cells at relapse, but imbalanced elevation of serum levels of free light chains was observed without changes in other clinical biomarkers including immunoglobulin levels. Salvage chemotherapy with isatuximab, pomalidomide, and dexamethasone (IsaPD) was promptly initiated. After two courses of IsaPD, significant remission was achieved and the neuronal symptoms completely resolved. When excessive serum levels of clonotypic free light chains are noted, their significance should be carefully assessed even when plasma cell propagation in the bone marrow is not observed. In such cases, hematologists should search for extramedullary proliferation of plasma cells, including in the immune-privileged central nervous system.

Primary plasma cell leukemia in Latin America: demographic, clinical, and prognostic characteristics. A study of GELAMM group.

Primary plasma cell leukemia (pPCL) is an infrequent and aggressive plasma cell disorder. The prognosis is still very poor, and the optimal treatment remains to be established. A retrospective, multicentric, international observational study was performed. Patients from 9 countries of Latin America (LATAM) with a diagnosis of pPCL between 2012 and 2020 were included. 72 patients were included. Treatment was based on thalidomide in 15%, proteasome inhibitors (PI)-based triplets in 38% and chemotherapy plus IMIDs and/or PI in 29%. The mortality rate at 3 months was 30%. The median overall survival (OS) was 18 months. In the multivariate analysis, frontline PI-based triplets, chemotherapy plus IMIDs and/or PI therapy, and maintenance were independent factors of better OS. In conclusion, the OS of pPCL is still poor in LATAM, with high early mortality. PI triplets, chemotherapy plus IMIDs, and/or PI and maintenance therapy were associated with improved survival.

How We Manage Newly Diagnosed Multiple Myeloma With Circulating Tumor Cells.

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Careful evaluation of peripheral blood for the presence of circulating plasma cells by morphologic assessment or by flow cytometric analysis is an essential component of the diagnostic workup in all patients with newly diagnosed multiple myeloma (MM) to timely differentiate between MM and primary plasma cell leukemia (pPCL), which is the most aggressive plasma cell dyscrasia. The improvement in survival over time is more modest in pPCL, compared with what has been achieved in MM. pPCL is currently defined by the presence of ≥ 5% circulating plasma cells. However, this cutoff is now challenged by new data, from three large cohorts of patients with newly diagnosed MM, showing that a threshold of 2% circulating tumor cells (CTCs) by flow cytometry can be used to identify a subset of patients with ultra-high-risk MM with comparable prognosis as patients with pPCL. These patients may benefit from more intensified first-line therapies, or from enrollment into specific clinical trials, designed for ultra-high-risk MM and pPCL. Apart from differentiating MM from pPCL, the quantification of CTCs is also useful for risk stratification in MM. The detection of CTCs above a threshold of 0.01%-0.07% (much lower than the threshold to define pPCL) appears to be an independent predictor of poor clinical outcomes in newly diagnosed MM. Additional studies, including transplant-ineligible patients or with incorporation of novel immunotherapies, are needed to identify a definitive prognostic CTC cutoff. The next step will be the incorporation of CTC detection into existing staging systems to improve risk stratification and treatment personalization.

Comparison of autologous and allogeneic hematopoietic cell transplantation strategies in patients with primary plasma cell leukemia, with dynamic prediction modeling.

Primary plasma cell leukemia (pPCL) is a rare and challenging malignancy. There are limited data regarding optimum transplant approaches. We therefore undertook a retrospective analysis from 1998-2014 of 751 patients with pPCL undergoing one of four transplant strategies; single autologous transplant (single auto), single allogeneic transplant (allo-first) or a combined tandem approach with an allogeneic transplant following an autologous transplant (auto-allo) or a tandem autologous transplant (auto-auto). To avoid time bias, multiple analytic approaches were employed including Cox models with time-dependent covariates and dynamic prediction by landmarking. Initial comparisons were made between patients undergoing allo-first (n=70) versus auto-first (n=681), regardless of a subsequent second transplant. The allo-first group had a lower relapse rate (45.9%, 95% confidence interval [95% CI]: 33.2-58.6 vs. 68.4%, 64.4-72.4) but higher non-relapse mortality (27%, 95% CI: 15.9-38.1 vs. 7.3%, 5.2-9.4) at 36 months. Patients who underwent allo-first had a remarkably higher risk in the first 100 days for both overall survival and progression-free survival. Patients undergoing auto-allo (n=122) had no increased risk in the short term and a significant benefit in progression-free survival after 100 days compared to those undergoing single auto (hazard ratio [HR]=0.69, 95% CI: 0.52- 0.92; P=0.012). Auto-auto (n=117) was an effective option for patients achieving complete remission prior to their first transplant, whereas in patients who did not achieve complete remission prior to transplantation our modeling predicted that auto-allo was superior. This is the largest retrospective study reporting on transplantation in pPCL to date. We confirm a significant mortality risk within the first 100 days for allo-first and suggest that tandem transplant strategies are superior. Disease status at time of transplant influences outcome. This knowledge may help to guide clinical decisions on transplant strategy.

Validation of the revised diagnostic criteria for primary plasma cell leukemia by the Korean Multiple Myeloma Working Party.

The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum ß2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis.

The clinical characteristics and prognosis of patients with primary plasma cell leukemia (pPCL) according to the new IMWG definition criteria.

Recently, the definition of primary plasma cell leukemia (pPCL) has been revised as the presence of circulating plasma cells (CPCs) ≥5% in peripheral blood smear. Consequently, the clinical features and prognosis of this aggressive disease can be truly identified by the larger patient cohort. Herein, we identified 158 new-defined pPCL patients among 2,266 MM patients (7.0%), and such prevalence doubled the previous estimate. Our study firstly provided solid support for the application of the new definition. We also found that cytopenias and adverse prognostic biomarkers were more common in new-defined pPCL compared with MM (p < 0.05). Besides, the patients receiving proteasome inhibitors based regimen in combination with stem cell transplantation could experience a considerable survival benefit. Strikingly, we showed that the presence of conventional high-risk cytogenetic abnormalities in pPCL didn't exert a great prognostic effect like MM, while elevated LDH reflecting tumor cells proliferation rate was the only independent predictor.

Plasma cell leukemia: Retrospective review of cases at Monter Cancer Center/Northwell Health Cancer Institute, 2014-2019.

Plasma cell leukemia (PCL) is an aggressive malignancy and an area of unmet need. The diagnostic criteria for PCL are in flux and the molecular basis of disease is complex. Due to its fulminant course and lack of prospective clinical trials in PCL, the optimal therapeutic approach remains controversial. "Novel therapy" in this manuscript refers to immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs). "Newer agents" refers to currently approved and investigational targeted therapies such as monoclonal antibodies (mAbs), example daratumumab (Dara), bi- or tri-specific antibodies, and antibody-drug conjugate therapies (ADCs). Novel therapy and use of newer agents borrowed from treatment advances in multiple myeloma (MM), is impacting PCL outcomes. Therefore, it is crucial to analyze effects of newer agents on PCL survival with respect to disease characteristics and specific treatment regimens used. In this retrospective study, we report outcomes of eight cases of PCL, primary and secondary, the prognostic factors in each case and the impact of different treatment regimens on overall survival (OS).

Plasma cell leukemia: A review of the molecular classification, diagnosis, and evidenced-based treatment.

Plasma cell leukemia is a rare and aggressive plasma cell dyscrasia associated with dismal outcomes. It may arise de novo, primary plasma cell leukemia, or evolve from an antecedent diagnosis of multiple myeloma, secondary plasma cell leukemia. Despite highly effective therapeutics, survival for plasma cell leukemia patients remains poor. Molecular knowledge of plasma cell leukemia has recently expanded with use of gene expression profiling and whole exome sequencing, lending new insights into prognosis and therapeutic development. In this review, we describe the molecular knowledge, clinical characteristics, evidenced-based therapeutic approaches and treatment outcomes of plasma cell leukemia.

Clinical Characteristics and Outcomes of Patients With Primary Plasma Cell Leukemia in the Era of Novel Agent Therapy.

OBJECTIVE: To evaluate the clinical outcomes of patients with primary plasma cell leukemia (pPCL) defined by 5% or greater clonal circulating plasma cells on peripheral blood smear and treated with novel agent induction therapies. PATIENTS AND METHODS: A cohort of 68 patients with pPCL diagnosed at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, to December 31, 2019, and treated with novel agent induction therapies was evaluated. RESULTS: The median follow-up was 46 (95% CI, 41 to 90) months. The median bone marrow plasma cell content was 85% (range, 10% to 100%) and median clonal circulaitng plasma cell percentage on the peripheral blood smear was 26% (range, 5% to 93%). There was a preponderance of t(11;14) primary cytogenetic abnormality in this cohort. The median time to next therapy (TTNT) and overall survival (OS) for all patients with pPCL patients in this cohort was 13 (95% CI, 9 to 17) and 23 (95% CI, 19 to 38) months, respectively. However, when stratified by cytogenetic risk, the median TTNT and OS were 16 and 51 months for standard risk vs 9 and 19 months for high risk (P=.01 for OS). CONCLUSION: Primary plasma cell leukemia remains an aggressive disease with poor prognosis despite novel agent-based therapies. Some patients have better than expected survival and this phenomenon may be influenced by the absence of high-risk cytogenetics. Newer treatment regimens are needed to improve the prognosis of this devastating disease.

A clinical perspective on plasma cell leukemia; current status and future directions.

Primary plasma cell leukemia (pPCL) is an aggressive plasma cell disorder with a guarded prognosis. The diagnosis is confirmed when peripheral blood plasma cells (PCs) exceed 20% of white blood cells or 2000/µL. Emerging data demonstrates that patients with lower levels of circulating (PCs) have the same adverse prognosis, challenging the clinical disease definition, but supporting the adverse impact of circulating PCs. The cornerstone of treatment consists of combination therapy incorporating a proteasome inhibitor, an immunomodulatory agent, steroids, and/or anthracyclines and alkylators as part of more-intensive chemotherapy, followed by consolidative autologous hematopoietic cell transplantation in eligible patients and then maintenance therapy. Monoclonal antibodies are also currently being evaluated in this setting with a strong rationale for their use based on their activity in multiple myeloma (MM). Due to limited therapeutic studies specifically evaluating pPCL, patients with pPCL should be considered for clinical trials. In contrast to MM, the outcomes of patients with pPCL have only modestly improved with novel therapies, and secondary PCL arising from MM in particular is associated with a dismal outlook. Newer drug combinations, immunotherapy, and cellular therapy are under investigation, and these approaches hopefully will demonstrate efficacy to improve the prognosis of pPCL.

A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma.

B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR-exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell-associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.

Successful upfront cord blood transplantation for plasma cell leukemia in the first complete response after daratumumab therapy.

Plasma cell leukemia (PCL) is a rare and aggressive disease with a poor prognosis. Autologous or allogeneic stem cell transplantation (ASCT or allo-SCT) with intensive chemotherapy is performed for PCL, but their efficacy is still controversial. The efficacy of novel agents such as daratumumab for PCL is also unclear. Here, we report a case of PCL treated successfully with daratumumab and upfront cord blood transplantation (CBT) in the first complete response (CR). A 58-year-old man was diagnosed with PCL based on elevated abnormal plasma cells and IgD levels. After two cycles of bortezomib, lenalidomide, and dexamethasone therapy, some PCL cells remained in the bone marrow. We switched treatment to daratumumab, lenalidomide, and dexamethasone therapy and confirmed an immunophenotypic CR. We then performed CBT with fludarabine, melphalan, and total body irradiation for conditioning 3 months after diagnosis. Acute graft-versus-host disease was observed but controlled with corticosteroid therapy. The patient remained in stringent CR for 1 year after CBT. We successfully treated PCL with daratumumab followed by upfront CBT. Daratumumab was effective in PCL and could be used safely even before allo-SCT. Early use of daratumumab and early upfront allo-SCT may be a useful treatment option for PCL.

Single-Cell Transcriptomic Analysis Reveals BCMA CAR-T Cell Dynamics in a Patient with Refractory Primary Plasma Cell Leukemia.

Chimeric antigen receptor T cell (CAR-T) therapy has revolutionized the clinical treatment of hematological malignancies due to the prominent anti-tumor effects. B cell maturation antigen (BCMA) CAR-T cells have demonstrated promising effects in patients with relapsed/refractory multiple myeloma. However, the dynamics of CAR-T cell proliferation and cytotoxicity in clinical patients remains unexplored. Here, we longitudinally profiled the transcriptomes of 55,488 T cells including CAR-T products, CAR-T cells, and endogenous T cells at the peak and remission phases in a plasma cell leukemia (PCL) patient treated with BCMA CAR-T cells by single-cell transcriptomic analysis. Our results showed distinct CAR-T and endogenous T cell subsets indicating stage-specific expression in proliferation, cytotoxicity, and intercellular signaling pathways. Furthermore, we found that CAR-T cells at peak phase gradually convert to a highly cytotoxic state from a highly proliferative state along a development trajectory. Moreover, re-analysis of a single cell study from CD8+ CD19 CAR-T confirmed our findings. These commonalities suggest conserved mechanisms for CAR-T treatment across hematological malignancies. Taken together, our current study provides insight into CAR-T cell dynamics during CAR-T therapy and proves that both BCMA CAR-T and CD19 CAR-T have similar transcriptional characteristics, especially at the CAR-T peak phase.