CAR T-Cell Therapy Demonstrates Efficacy in Transplant-Ineligible Patients with LBCL

TOP - September 2022 Vol 15, No 5 - Lymphoma

More than 50% of adults with refractory or relapsed large B-cell lymphoma (LBCL) who were not deemed candidates for high-dose chemotherapy and hematopoietic stem-cell transplantation (HSCT) had complete responses (CRs) following treatment with the chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (Breyanzi).

In the phase 2 PILOT clinical trial, the overall response rate (ORR) with lisocabtagene maraleucel was 80% and the rate of CR was 54%, with a median follow-up of 12.3 months, reported Alison Sehgal, MD, Assistant Professor, Medicine, University of Pittsburgh Medical Center, Hillman Cancer Center, PA, and colleagues, in a poster presentation at the 2022 American Society of Clinical Oncology Annual Meeting. The responses in patients who achieved a CR were durable, with a median duration of response of 21.7 months.

“These results support liso-cel [lisocabtagene maraleucel] as a second-line treatment in patients with LBCL in whom HSCT is not intended,” the investigators stated.

For patients who are unable to have high-dose therapy or HSCT, there is no effective established standard of care and outcomes are historically poor, the investigators noted in laying out the rationale for the study.

Study Details

The open-label, multicenter PILOT study enrolled a broad patient population of adults with refractory or relapsed LBCL after first-line treatment who were not considered candidates for HSCT based on age ≥70 years, Eastern Cooperative Oncology Group performance status of 2 and/or organ function, and comorbidities such as depressed left ventricular ejection fraction, a creatinine clearance <60 mL/min, or elevated levels of liver enzymes, regardless of time to relapse following first-line treatment.

A total of 74 patients underwent leukapheresis, 61 of whom received lisocabtagene maraleucel and were included in the safety and efficacy analysis. In all, 32 patients (52%) received bridging therapy before lymphodepletion and lisocabtagene maraleucel infusion. A total of 28 patients have discontinued the study, 20 of whom died. Treatment is ongoing in 26 patients. Of the patients treated with lisocabtagene maraleucel, 20 (33%) met ≥2 of the 6 protocol-specified criteria for ineligibility for transplant. Of the 61 patients who received lisocabtagene maraleucel, 20 were monitored in the outpatient setting.

The median patient age was 74 years. The LBCL histology was diffuse LBCL in 54%, transformed follicular lymphoma (FL) in 15%, high-grade B-cell lymphoma with LBCL histology in 30%, and grade 3B FL in 2%. In all, 54% of the patients had refractory LBCL, 21% relapsed after ≤12 months, and 25% relapsed after >12 months. Patients could receive multiple regimens as first-line treatment. First-line treatment for LBCL was R-CHOP (rituximab [Rituxan] plus cyclophosphamide, doxorubicin, vincristine, and prednisone) in 84% of patients, R-EPOCH (rituximab plus etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) in 16%, R-ICE (rituximab plus ifosfamide [Ifex], carboplatin, and etoposide), R-CHP (rituximab plus cyclophosphamide, doxorubicin, and prednisone), and/or other treatment in 13%, and 11% of the patients received radiotherapy. The best response to first-line therapy for LBCL was a CR in 46% of the patients and a partial response in 25%.

The median duration of response in the overall population at a median follow-up of 15.5 months was 12.1 months. The median progression-free survival (PFS) was 9 months (95% confidence interval [CI], 4.2-not reached [NR]), and the median overall survival has not been reached (95% CI, 17.3-NR).

The screening Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in patients who received lisocabtagene maraleucel was 2 in 56% of patients and 3 in 44%. The ORR by the HCT-CI total score was 79% for patients with an HCT-CI of <3 and 81% in those with an HCT-CI of ≥3, with CR rates of 17% and 16%, respectively. The median duration of response in these 2 groups was 11.2 months and not reached, respectively, and the median PFS was 7.4 months and not reached, respectively.

The safety profile of lisocabtagene maraleucel was manageable, with no new safety signals and low rates of severe cytokine release syndrome (CRS) or neurologic events, and no grade 4 or 5 CRS or neurologic events reported. Any-grade CRS occurred in 38% of patients, with grade 3 CRS reported in 1 (2%) patient.

In a separate analysis of patient-reported outcomes (PROs), patients who received lisocabtagene maraleucel and were evaluable for the PRO analysis (N = 56) showed significant improvements in fatigue and pain. Improvements in overall lymphoma symptoms were clinically meaningful after treatment; in an individual patient-level analysis, 70% of patients reported meaningful improvements in quality of life.

FDA Approval Update

Lisocabtagene maraleucel was approved by the FDA for the treatment of relapsed or refractory LBCL after nonresponse to first-line therapy on June 24, 2022. This approval was granted with priority review and received regenerative medicine advanced therapy, breakthrough therapy, and orphan drug designations (see here).

Related Items
Trastuzumab Deruxtecan Represents New Standard of Care for Patients with HER2-Low Metastatic Breast Cancer
William King
TOP - September 2022 Vol 15, No 5 published on September 15, 2022 in Breast Cancer
Darolutamide plus ADT and Docetaxel Improves Survival in Men with Metastatic Hormone-Sensitive Prostate Cancer
William King
TOP - September 2022 Vol 15, No 5 published on September 15, 2022 in Prostate Cancer
ASCO President Stresses the Importance of Innovation for Advancing Equitable Cancer Care
William King
TOP - September 2022 Vol 15, No 5 published on September 15, 2022
High-Risk Localized Renal-Cell Carcinoma May Benefit from Neoadjuvant Combination of Avelumab and Axitinib
William King
TOP - September 2022 Vol 15, No 5 published on September 15, 2022 in Renal-Cell Carcinoma
Experts Discuss the Evolving Role of Telemedicine in Oncology Care
William King
TOP - July 2022 Vol 15, No 4 published on July 20, 2022 in Telemedicine
Ibrutinib Added to Standard-of-Care Therapy Improves Progression-Free Survival in Older Patients with MCL
William King
TOP - July 2022 Vol 15, No 4 published on July 20, 2022 in ASCO 2022 Highlights
Updated NCCN Guidelines Lower Age for Initial Colorectal Cancer Screening
William King
TOP - May 2022 Vol 15, No 3 published on May 6, 2022 in NCCN 2022 Highlights
Pembrolizumab Added to Best Supportive Care Extends Survival in Patients with Hepatocellular Carcinoma
William King
TOP - May 2022 Vol 15, No 3 published on May 6, 2022 in ASCO GI 2022 Highlights
Nivolumab plus Ipilimumab Yields High Rate of pCR in the Neoadjuvant Setting for Patients with Resectable MSI/dMMR Oeso-Gastric Adenocarcinoma
William King
TOP - May 2022 Vol 15, No 3 published on May 6, 2022 in ASCO GI 2022 Highlights
Trastuzumab Deruxtecan Shows Survival Benefit in HER2-Positive Advanced Gastric Cancers
William King
TOP - May 2022 Vol 15, No 3 published on May 6, 2022 in ASCO GI 2022 Highlights
Last modified: September 16, 2022