Beijing GoBroad Boren Hospital| Expert Perspective | Director Hu Kai: What You Need to Know About CAR-T Therapy for Malignant Lymphoma & Multiple Myeloma
- Elva Chen
- Jul 28
- 3 min read
For patients with Diffuse Large B-Cell Lymphoma (DLBCL) resistant to the R-CHOP regimen (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone), long-term survival prospects remain poor regardless of clinical stage or genetic risk stratification. Novel therapies are urgently needed to improve long-term outcomes for these relapsed/refractory patients.
1. Clinical Trials of CAR-T for R/R DLBCL
CAR-T therapy has achieved remarkable success in relapsed/refractory acute lymphoblastic leukemia, and delivers promising efficacy for DLBCL. Key global landmark trials are summarized below:
ZUMA Trial
The earliest pivotal CAR-T trial for R/R DLBCL, utilizing CD19-targeted CAR-T with CD28 costimulatory domain. The ZUMA series has advanced to ZUMA 9 and real-world research, enrolling over 295 patients. Key findings: CD28-based CAR-T triggers rapid, severe cytokine release syndrome (CRS); 32% of patients required ICU admission for CRS. Re-administering identical CAR-T cells to partial response (PR) patients fails to boost efficacy.
JULIET Trial
A global multicenter trial adopting CAR-T with 4-1BB costimulatory domain, which demonstrated milder adverse reactions compared to CD28-based constructs.
Outstanding challenges remain for CAR-T in R/R DLBCL: optimal timing of CAR-T intervention, higher complete remission (CR) rates, long-term disease control post-remission, and standardized clinical management of CRS toxicity.
2. Clinical Outcomes of CAR-T for Lymphoma & Myeloma at Our Adult Lymphoma Department
Our team conducts multiple immunotherapy programs: CD19 CAR-T for R/R B-cell malignancies, sequential CD19/CD22 CAR-T for R/R DLBCL, and BCMA CAR-T for relapsed/refractory multiple myeloma.
Patient Profile
Treated patients include DLBCL, Burkitt lymphoma, follicular lymphoma and multiple myeloma, mostly stage III/IV with heavily pretreated histories (average 10 chemotherapy cycles). Many relapsed after autologous stem cell transplantation or prior CAR-T therapy elsewhere, presenting progressive disease at admission with high clinical difficulty.
Therapeutic Efficacy
Early CR rate reaches 64%, overall response rate ~70%. Multiple myeloma achieves superior outcomes; heavily pretreated, rapidly progressive DLBCL and Burkitt lymphoma show suboptimal responses.
Safety Profile
Overall CRS incidence: ~80%; 70% grade I–II, only 13.20% severe grade III–IV. Median CRS onset day 5 (range 1–11).
Representative Case Reports
Case 1: Diffuse Large B-Cell Lymphoma
Non-germinal center DLBCL, stage IVB. The patient achieved PR after 4 cycles of R-CHOP, then complete remission after R2-CHOP and autologous stem cell transplant, maintained with lenalidomide consolidation. Three months prior to admission, recurrent abdominal mass (6.7cm×8.4cm×7.1cm), bilateral pulmonary and left renal nodules developed. GDP chemotherapy failed to control progression, accompanied by fever, emaciation, jaundice, partial intestinal obstruction and gastrointestinal hemorrhage.
Direct CAR-T infusion carried high risks of massive gastrointestinal bleeding and severe pulmonary CRS. We first controlled hemorrhage and obstruction with debulking conditioning chemotherapy, then administered murine CD19 CAR-T with standardized CRS supportive care. All symptoms resolved post-infusion; PET-CT at day 60 confirmed full clearance of primary lesions.
Case 2: Multiple Myeloma
Elderly male with 10-year history of IgG-Kappa multiple myeloma. Attained CR after PAD/VAD chemotherapy and autologous transplantation, maintained with lenalidomide plus 8 cycles of CIK cell therapy. Disease progressed later despite multiple lines of treatment (PCD, PRD, chidamide, carfilzomib, anti-CD38 monoclonal antibody, pomalidomide). Lumbar extramedullary plasmacytoma developed, complicated by pulmonary fungal infection and coronary stent implantation. Admission tests revealed 52% abnormal plasma cells in bone marrow, 14.85% BCMA-positive plasma cells, plus TP53/KRAS mutations.
We administered reduced-dose conditioning chemotherapy and split BCMA CAR-T infusion on day 1 and day 14 to mitigate toxicity. Only grade 1 fever occurred as CRS. At day 30 and 46 post-infusion, IgG levels normalized, bone marrow plasma cells turned negative, and PET-CT showed full resolution of extramedullary lesions.
Summary & Future Research Directions
Individualized debulking regimens for patients with high tumor burden before CAR-T infusion;
Combined and sequential multi-target CAR-T strategies to enhance efficacy;
Standardized minimal residual disease (MRD) monitoring to guide post-remission maintenance therapy.
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