Feasibility of post-induction consolidation with BCMA CAR-T cell therapy in newly diagnosed multiple myeloma not proceeding to ASCT: A preliminary case series

Abstract

B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy has demonstrated promising efficacy in relapsed/refractory multiple myeloma (MM). However, evidence supporting its use in earlier treatment settings remains limited. This study presents a preliminary case series evaluating the feasibility of BCMA CAR-T cell therapy as post-induction consolidation in newly diagnosed multiple myeloma (NDMM) patients who did not proceed to autologous stem cell transplantation (ASCT). Four patients were included in this analysis. After induction therapy, all patients achieved very good partial response or better and did not proceed to ASCT due to ineligibility or personal preference. They subsequently received BCMA CAR-T cell therapy as consolidation treatment. All patients tolerated the BCMA CAR-T cell infusion well. Cytokine release syndrome occurred in all cases, but was limited to grades 1–2, and no immune effector cell–associated neurotoxicity syndrome was observed. Following therapy, patients maintained or further deepened responses and ultimately reached stringent complete response (sCR) and minimal residual disease (MRD) negativity. During a median follow-up period of 17.8 months, all patients remained in sCR status and MRD negativity without the need for additional anti-tumor therapy, and none experienced relapse or disease progression. These preliminary results suggest that BCMA CAR-T cell therapy as post-induction consolidation is feasible and associated with manageable toxicity in NDMM patients not proceeding to ASCT, warranting further evaluation in larger prospective studies.

Keywords

newly diagnosed multiple myeloma CAR-T cell therapy BCMA post-induction consolidation case series

Introduction

Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells and the overproduction of monoclonal immunoglobulins, leading to organ damage, including bone lesions, renal dysfunction, anemia, and hypercalcemia¹. First-line induction therapies for newly diagnosed multiple myeloma (NDMM) typically involve combinations of proteasome inhibitors, immunomodulatory drugs, and corticosteroids. The overall response rate (ORR) generally exceeds 80%, with approximately 40%–50% of patients achieving at least a very good partial response (VGPR), and the response rate can increase by an additional 10%–20% following consolidation with autologous stem cell transplantation (ASCT)². However, a proportion of patients do not proceed to ASCT owing to transplant ineligibility (TI) or personal preference to defer transplantation. These individuals may face an increased risk of mortality and treatment-emergent adverse events, particularly among the frail elderly or those with high-risk cytogenetics^3,4. For patients who are not candidates for transplantation, current frontline treatments typically include triplet (such as DRd and VRD) or quadruplet (such as Dara-VRD and Isa-VRD) regimens^5–8. However, these strategies generally require prolonged treatment cycles, which may lead to cumulative toxicity, treatment burden, and financial costs^7–9. Therefore, there remains a need for alternative strategies that may improve disease control while reducing long-term treatment burden in NDMM patients who do not proceed to ASCT.

B-cell maturation antigen (BCMA) is a transmembrane glycoprotein that is highly and selectively expressed on malignant plasma cells, making it a promising target for immunotherapeutic intervention in MM, especially in relapsed/refractory (R/R) cases¹⁰. BCMA chimeric antigen receptor (CAR)-T cell therapy has demonstrated satisfactory efficacy and controllable toxicities in heavily pretreated R/R MM patients^11,12. In a phase II study of idecabtagene vicleucel (ide-cel), the overall response rate (ORR) was 73%, with 33% of patients achieving complete response (CR) or better, and a median progression-free survival (PFS) of 8.8 months¹². Similarly, ciltacabtagene autoleucel (cilta-cel) achieved an ORR of 97%, with 67% of patients reaching stringent complete response (sCR), and 12-month PFS and overall survival (OS) rates of 77% and 89%, respectively¹¹. These promising results have led to the approval of several commercial BCMA CAR-T products for clinical use. More recently, interest has emerged in evaluating CAR-T therapy in earlier lines of treatment, including as a consolidation strategy in patients who do not proceed to ASCT. Early clinical observations, including case reports and preliminary trial data, suggest that this approach may be feasible and associated with deep responses in selected patients^13,14.

Here, we report a preliminary case series of four NDMM patients who received BCMA CAR-T cell therapy as post-induction consolidation. Disease responses were maintained or further deepened following therapy, all patients ultimately reached sCR and minimal residual disease (MRD) negativity without experiencing severe toxicity. These results support the feasibility of BCMA CAR-T cell therapy as post-induction consolidation in NDMM patients not undergoing ASCT.

Methods

We analyzed the clinical data of four NDMM patients who received commercial BCMA CAR-T cell therapy (Zevorcabtagene Autoleucel, Zevor-cel) as post-induction consolidation treatment at our institution between January 2024 and February 2026. This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology (No.: TJ-IRB202510067; Date of approval: 29 October 2025). All patients provided written informed consent for treatment and publication of their clinical details. All cases met the diagnostic criteria of the International Myeloma Working Group (IMWG)¹⁵. Clinical staging was determined using the Durie–Salmon (DS) and Revised International Staging System (R-ISS). Frailty was assessed according to the IMWG frailty scoring system.

Patients completed at least four cycles of induction therapy and were ineligible for ASCT or preferred to defer transplantation. Transplant ineligibility was defined as advanced age (≥65 years), poor performance status (ECOG 3–4), significant comorbidities, and repeated mobilization failure. All patients underwent leukapheresis for the collection of peripheral blood mononuclear cells. The harvested cells were subsequently transported to the CARsgen Therapeutics manufacturing facility for BCMA CAR-T cell production. The manufacturing process, quality control, and product release were performed by CARsgen Therapeutics in accordance with regulatory requirements.

Prior to CAR-T infusion, patients received a lymphodepleting conditioning regimen consisting of fludarabine and cyclophosphamide, as previously described¹⁶. After therapy, efficacy was assessed at 1 month, 3 months, and periodically thereafter, according to the IMWG 2016 criteria¹⁵. Treatment response was categorized as sCR, CR, VGPR, partial response (PR), stable disease (SD), or progressive disease (PD). PFS was defined as the time interval from CAR-T cell infusion to disease progression, death, or the last follow-up point. OS was defined as the time from CAR-T cell infusion to death or the follow-up endpoint. MRD was assessed through bone marrow (BM) aspiration using standardized Euroflow cytometry, with a sensitivity threshold of 10⁻⁵ nucleated cells. Peripheral blood CAR transgene copy numbers were dynamically monitored via droplet digital polymerase chain reaction. Safety assessments included monitoring for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), both graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria¹⁷. Hematologic events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. The data cutoff date for this study was February 2026.

Results

Baseline characteristics

This analysis included four male patients newly diagnosed with MM, aged between 44 and 76 years. Patient 1 had the IgA-κ subtype, while the other three presented with the IgG-λ subtype. According to the DS staging system, one patient was classified as stage III, one as stage II, and two as stage I. Based on the R-ISS staging system, three patients were classified as stage II, and one patient as stage I. None of the patients exhibited evidence of extramedullary disease. BM plasma cell infiltration varied among patients, with values ranging from 5 to 40%. Serum β2-MG levels ranged from 1.59 to 4.89 mg/l, and lactate dehydrogenase (LDH) levels were within normal limits in all patients (range: 143–227 U/l). Frailty assessment showed that patient 1 was frail, patient 3 was intermediate-fit, and patients 2 and 4 were fit. Cytogenetic analysis revealed the presence of 1q21 gain in three patients (patients 1–3), while no detectable cytogenetic abnormalities were found in patient 4. Additional baseline characteristics are summarized in Table 1.

Table 1.

Baseline characteristics of the patients.

	Patient 1	Patient 2	Patient 3	Patient 4
Sex/Age	Male/76	Male/49	Male/46	Male/44
Presenting symptoms	Renal insufficiency	Anemia	Headache	Fever
Myeloma type	IgA-κ	IgG-λ	IgG-λ	IgG-λ
Hemoglobin (g/l)	124	82	118	144
Calcium (mmol/l)	2.4	2.02	2.13	2.23
Creatinine (μmol/l)	164	93	151	77
β2-MG (mg/l)	2.77	3.12	4.89	1.59
LDH (U/l)	227	150	197	143
Extramedullary disease	No	No	No	No
BM plasma cells (%)	5	20	20	40
DS stage	I	III	II	I
R-ISS stage	II	II	II	I
High risk cytogenetic abnormality	gain (1q21)	gain (1q21)	gain (1q21)	Negative
ECOG score	2	1	2	1
IMWG frailty score	3 (Frail)	0 (Fit)	1 (Intermediate Fit)	0 (Fit)

β2-MG: Beta-2 Microglobulin; LDH: lactate dehydrogenase; BM: bone marrow; DS: Durie–Salmon Staging System; R-ISS: Revised International Staging System; ECOG: Eastern Cooperative Oncology Group; IMWG: International Myeloma Working Group.

Treatment and toxicity

All patients received induction therapies following their disease diagnosis. The induction regimens included four cycles of VRD for patient 1, a combination of two cycles of VRD and two cycles of BD for patient 2, six cycles of VCD for patient 3, and six cycles of VRD for patient 4 (Table 2). After induction therapy, all participants achieved at least a VGPR. However, these patients did not proceed to ASCT due to transplant ineligibility (Patient 1) or patient preference to defer transplantation (Patients 2–4). Furthermore, they declined long-term multi-drug consolidation and maintenance therapy due to concerns about cumulative toxicity and treatment burden, and therefore BCMA CAR-T cell therapy was proposed and accepted as exploratory post-induction consolidation.

Table 2.

Treatment and outcomes of the patients.

	Patient 1	Patient 2	Patient 3	Patient 4
Induction therapy	VRD × 4	VRD × 2; BD × 2	VCD × 6	VRD × 6
Reasons for not proceeding ASCT	Advanced age and frailty	Personal preference to defer ASCT	Personal preference to defer ASCT	Personal preference to defer ASCT
Disease status before CAR-T	VGPR	sCR MRD-negative	sCR	sCR
CAR-T cell dose (10⁸)	3.85	4.30	1.70	1.50
CRS	1	1	1	2
ICANS	None	None	None	None
Hematologic event (≤30 days)
Leukopenia	4	2	4	4
Neutropenia	4	4	4	4
Anemia	3	1	3	3
Thrombocytopenia	4	1	4	4
Hematologic event (>30 days)
Leukopenia	4	0	4	2
Neutropenia	4	0	4	3
Anemia	3	0	3	0
Thrombocytopenia	3	0	4	0
Infections	No	No	Yes	Yes
Follow-up time^a (month)	22.9	19.0	16.6	16.3
Long-term outcomes	sCR MRD-negative	sCR MRD-negative	sCR MRD-negative	sCR MRD-negative

VRD: bortezomib, lenalidomide, dexamethasone; VCD: bortezomib, cyclophosphamide, dexamethasone; BD: bortezomib; dexamethasone; ASCT: autologous stem cell transplantation; VGPR: very good partial response; sCR: stringent complete response; CAR-T: chimeric antigen receptor T cell therapy; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; MRD, minimal residual disease.

The data cutoff date was February 2026.

Before infusion, all patients received a 3-day lymphodepletion regimen with fludarabine and cyclophosphamide. BCMA CAR-T cells were administered at doses based on the total number of cultured cells, 3.85 × 10⁸, 4.30 × 10⁸, 1.70 × 10⁸, 1.50 × 10⁸ cells in patients 1–4, respectively. The interval between lymphocyte collection and CAR-T cell infusion ranged from 27 to 34 days. The most commonly reported adverse events associated with CAR-T cell therapy were CRS and ICANS. All patients experienced low-grade CRS after therapy. Only patient 4 developed grade 2 CRS, while the remaining patients had grade 1 CRS. No cases of severe CRS or any grades of ICANS were observed. Elevated levels of the pro-inflammatory cytokine interleukin-6 (IL-6) were detected following CAR-T cell infusion, with peak median concentrations reaching 176.25 pg/ml (range: 16.19–443.5) at the median of 8.5 (range: 2–15) days. These levels subsequently decreased to low or within normal range. All patients developed early hematologic toxicity (≤30 days) after CAR-T infusion, with universal grade 4 neutropenia. Grades 3–4 thrombocytopenia and anemia occurred in three patients. Beyond 30 days, recovery of cytopenia was heterogeneous, with abnormalities noted in selected cases (patients 1 and 3, Table 2). No patient required red blood cell transfusions, while only patient 3 required platelet transfusion support. Infectious complications occurred in patients 3 and 4 and improved with appropriate treatment.

CAR-T kinetics

All four patients exhibited significant variability in CAR-T cell expansion kinetics following infusion (Figure 1a). The peak number of CAR transgene copies ranged from 230 to 221,108 copies/μg DNA, with peak levels occurring from 5 to 39 days post-infusion. Patient 2 demonstrated the most robust expansion, with a peak of 221,108 copies/μg DNA on day 27, followed by sustained persistence until day 411 (399 copies/μg DNA), indicating long-term expansion and persistence of CAR-T cells in vivo. In contrast, expansion in patient 3 was more limited, reaching a peak of only 230 copies/μg DNA on day 5, followed by a rapid decline. Additionally, only patient 4 regularly monitored the proportion of CAR-T cells in peripheral blood, reaching a peak of 6.18% of total peripheral blood T cells on day 18.

Figure 1.

In vivo expansion kinetics of CAR-T cells and clinical course in patients. (a) CAR-T transgene copy number in peripheral blood over time in three patients (Patients 1, 2, and 4). The inset shows the proportion of CAR-T cells among total T cells in patient 4. (b) Swimmer plot of the clinical course of individual patients from diagnosis to last follow-up. The x-axis indicates days from diagnosis. Arrows denote ongoing response. VRD: bortezomib, lenalidomide, dexamethasone; VCD: bortezomib, cyclophosphamide, dexamethasone; BD: bortezomib; dexamethasone; VGPR: very good partial response; sCR: stringent complete response; MRD, minimal residual disease. The last follow-up was conducted on 28 February 2026.

Response and survival

Patient 1 was in VGPR status prior to treatment. At the first assessment (day 39 post-infusion), the patient maintained VGPR, followed by an improvement in response depth nearly 2 months after CAR-T cell therapy, achieving sCR and MRD negativity. Additionally, the three patients who already achieved sCR maintained their remission. Patient 2 remained MRD-negative, while patients 3 and 4 converted to MRD negativity at the first post-infusion assessment (Figure 1b). As of 28 February 2026, with a median follow-up time of 17.8 months (range: 16.3–22.9 months), all patients maintained sCR status and MRD negativity. The estimated 1-year OS and PFS rates were both 100%, and the median duration of response (DOR), PFS and OS have not yet been reached. To date, none of the patients have experienced MRD recurrence or disease progression, and no additional anti-tumor therapy has been required. Throughout the follow-up period, patients maintained stable performance status, and clinical assessments did not indicate any significant decline in daily functioning.

Discussion

In this study, four NDMM patients ineligible for or deferring ASCT received BCMA CAR-T cell therapy as post-induction consolidation. All patients achieved VGPR or better after induction therapy, and disease control was maintained or modestly deepened following CAR-T infusion, with no severe toxicities or disease progression observed during a median follow-up of 17.8 months. These preliminary findings suggest that BCMA CAR-T cell therapy as post-induction consolidation in NDMM patients not undergoing ASCT is feasible and warrants further investigation in larger prospective studies.

In patients with NDMM who are ineligible for transplantation due to age, performance status, or other reasons, current standard of care typically involves triplet regimens such as DRd or VRD, particularly for frail individuals¹⁸. DRd was approved for NDMM following a multinational randomized phase 3 trial that demonstrated its superiority over lenalidomide plus dexamethasone (Rd)¹⁹. Similarly, VRD has shown a survival advantage compared with Rd⁵. VRD is generally given for 8–12 cycles, followed by maintenance therapy, whereas DRd involves the continuous administration of all three agents until disease progression, making it a more costly long-term treatment option¹⁸. More recently, quadruplet regimens combining daratumumab or isatuximab with VRD have been explored as frontline therapies in TI NDMM patients. Clinical trial data indicated that Dara-VRD achieved CR or better in 81.2% of patients, with sustained MRD negativity (≥12 months) in 48.7%⁸. The Isa-VRD regimen resulted in CR or better in 58% of patients at 18 months, with 37% achieving both MRD negativity and CR or better⁷. Although these findings highlight the enhanced efficacy of quadruplet regimens, a proportion of patients still fail to achieve MRD negativity, which remains a critical predictor of long-term PFS and OS²⁰. Furthermore, quadruplet regimens are associated with substantial costs exceeding US$300,000 in the first 2 years⁹, along with an increased risk of cumulative toxicity. These factors may lead to treatment discontinuation and significantly impair patients’ quality of life.

In this study, four patients who did not proceed to ASCT received BCMA CAR-T therapy as exploratory post-induction consolidation. All patients maintained or further deepened their responses following treatment, without MRD recurrence or disease progression observed during a median follow-up of 17.8 months. These findings are generally consistent with preliminary data from early-phase clinical studies. For example, a phase II study presented at conference reported that consolidation with BCMA CAR-T cell therapy in TI NDMM patients was associated with high response rates, including an ORR of 100% and VGPR or better in 95% of patients. Notably, all patients achieved MRD negativity at a median follow-up of 7.1 months¹⁴. Together, these preliminary observations suggest that BCMA CAR-T cell therapy may induce or sustain disease responses in selected patients when applied in earlier lines of treatment. However, as all patients in our cohort had already achieved VGPR or better prior to infusion, the independent contribution of CAR-T therapy cannot be clearly determined. Currently, BCMA CAR-T cell therapy in earlier lines of NDMM treatment remains under active investigation. Several clinical trials (e.g., NCT07070960, NCT05860036, and NCT07114432) are evaluating its use as consolidation or early-line therapy in patients who are ineligible for or unwilling to undergo ASCT, while others are comparing or combining BCMA CAR-T therapy with ASCT in transplant-eligible patients (e.g., NCT06793449 and NCT06913192). These efforts reflect increasing interest in the role of BCMA CAR-T therapy in earlier treatment settings. Within this evolving field, our preliminary findings should be considered hypothesis-generating and interpreted with caution.

The potential clinical activity of CAR-T cell therapy as a consolidation strategy in NDMM may be supported by several key factors. First, following initial induction therapy, patients typically present with a lower tumor burden and relatively preserved immune function, which may provide a more favorable environment for CAR-T cell expansion and long-term persistence. Consistent with this, most patients in our study exhibited robust CAR-T cell expansion following infusion, which has been associated with improved clinical outcomes in previous reports^21–23. In addition, CAR-T cell consolidation may contribute to more effective clearance of residual disease, thereby increasing the possibility of achieving MRD negativity²⁴, a key predictor of long-term outcomes in MM. Notably, in a recent study of 14 patients with R/R MM treated with Zevor-cel, high response rates and durable remissions were observed, with a median duration of response of 24.94 months²⁵. Although these findings were obtained in a different disease setting, they provide supportive evidence for the sustained activity of this CAR-T product. Nevertheless, further follow-up is required to assess the durability of responses when Zevor-cel is used as post-induction consolidation in NDMM.

CRS and ICANS, the most common CAR-T cell-associated adverse effects, were generally mild in the current study and could be effectively managed with appropriate clinical interventions. No severe CRS or neurotoxicity occurred. These findings are consistent with previous reports in both consolidation and R/R settings. For example, CRS (grades 1–2) was observed in 75% (15/20) of patients, with only two cases of grade 1 ICANS reported during BCMA CAR-T consolidation¹⁴. Similarly, the LUMIERE study²⁵ demonstrated that Zevor-cel was associated with limited grades 1–2 CRS and no ICANS in patients with R/R MM. These data collectively suggest a manageable safety profile of Zevor-cel across disease stages. Furthermore, hematologic toxicities were common but generally transient and primarily associated with lymphodepleting chemotherapy. Overall, BCMA CAR-T cell therapy demonstrated a controllable toxicity profile in NDMM patients treated in the post-induction consolidation setting.

Economic considerations remain a critical factor due to the high costs and manufacturing complexities associated with CAR-T therapy^26,27. Nevertheless, ongoing technological advances and the increasing commercialization of this approach are expected to enhance its accessibility in the future. Innovations such as the development of universal CAR-T cells and the introduction of automated, closed-system manufacturing platforms represent major progress in overcoming the limitations of conventional manual processes^28,29. Accordingly, integrating BCMA CAR-T therapy into earlier treatment settings for NDMM is being actively explored. Such approaches may reduce reliance on prolonged multi-agent therapy and its associated cumulative toxicity, although further evidence is required to support this strategy. In addition, combination approaches involving CAR-T cells with monoclonal antibodies or other novel agents may further expand therapeutic options.

The limitations of this study are as follows. First, this study was conducted in a highly selected NDMM cohort not undergoing ASCT; therefore, the findings are not generalizable to the broader frontline population. In addition, the small sample size, limited follow-up time, and pre-existing disease responses prior to CAR-T cell infusion limit the interpretation of the independent contribution of CAR-T therapy. Further validation in larger prospective studies with longer follow-up is required to better define the safety, efficacy, and optimal role of BCMA CAR-T cell therapy in earlier treatment settings.

Conclusion

In conclusion, these preliminary findings suggest that BCMA CAR-T cell therapy may be feasible as post-induction consolidation in NDMM patients not undergoing ASCT, with manageable toxicity and maintenance or modest deepening of pre-existing response observed in this small cohort. This strategy may represent a potential option for TI patients or those deferring transplantation. However, these preliminary findings are hypothesis-generating and do not provide definitive evidence of efficacy. Further validation in larger prospective studies is required.

Footnotes

Acknowledgements

Not available.

ORCID iDs

Jiaying Wu

Xi Ming

Yi Xiao

Ethical considerations

This study was approved by the Ethics Committee of Tongji Hospital, Tongji Medical College, and Huazhong University of Science and Technology (No. TJ-IRB202510067; Date of approval: 29 October 2025).

Consent to participate

All patients provided written informed consent to participate in this study.

Consent for publication

All patients provided written informed consent for the publication of their clinical data.

Author contributions

J.W. and R.Z. contributed to data analysis and manuscript writing. X.M. was responsible for clinical data collection. X.Z. revised the manuscript prior to submission. M.Z. and Y.X. contributed to the conception of the study and provided funding support.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Natural Science Foundation of China (No. 82370196), and Tongji Hospital Funding(2024B18).

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Data availability statement

The datasets during the current study are available from the corresponding author on reasonable request.

Artificial intelligence (AI) statement

The authors confirm that no AI tools were used in this manuscript, and take full responsibility for the accuracy and integrity of all content.

Statement of human and animal rights

The study involved human participants and was conducted in accordance with the Declaration of Helsinki. No animal subjects were involved in this study.

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