Clinical Scorecard: Combination of Lisaftoclax, Ixazomib, and Dexamethasone for Maintenance Therapy Following CAR-T in Patients with Transplant-Ineligible Relapsed/Refractory Ultra-High-Risk Multiple Myeloma

At a Glance

Key Highlights

• ILD regimen (ixazomib, lisaftoclax, dexamethasone) administered orally in 28-day cycles post-CAR-T therapy.
• Achieved durable disease control with sustained MRD negativity in two reported UHR MM cases.
• Lisaftoclax shows higher BCL-2 binding affinity and lower off-target effects compared to traditional BCL-2 inhibitors, suitable for long-term maintenance.

Guideline-Based Recommendations

Diagnosis

• Use 2026 IMWG Response Criteria for MM including CR, VGPR, PR, SD, PD.
• Assess MRD by 8-color multiparameter flow cytometry (sensitivity 10^-5), protein electrophoresis, and 18F-FDG PET/CT imaging.
• Define UHR MM by ≥2 high-risk cytogenetic abnormalities or TP53 biallelic deletion/mutation per mSMART 3.0 and 2024 Chinese guidelines.

Management

• Administer ixazomib 4 mg on days 1, 8, and 15; lisaftoclax 400 mg on days 1–14; dexamethasone 20 mg on days 1, 8, and 15 in 28-day cycles.
• Discontinue treatment upon uncontrollable active infection or organ injury.
• Consider ILD combination therapy as a maintenance option post-CAR-T for relapsed/refractory UHR MM.

Monitoring & Follow-up

• Regular MRD assessment by flow cytometry, serum/urine protein electrophoresis, and PET/CT imaging at intervals ≥1 month.
• Monitor adverse events per CTCAE v5.0 with dose adjustments or interruptions as needed.
• Track treatment response and toxicity to optimize therapy duration and safety.

Risks

• Potential adverse events requiring dose reduction or treatment interruption.
• Risk of active infection or organ injury necessitating treatment discontinuation.
• Limited data from small case series; formal evaluation in larger cohorts needed.

Patient & Prescribing Data

Two transplant-ineligible patients with relapsed/refractory ultra-high-risk multiple myeloma post-BCMA CAR-T therapy.

ILD regimen achieved durable MRD negativity and disease control with manageable safety profile, suggesting a promising maintenance strategy for difficult-to-treat MM.

Clinical Best Practices

• Use comprehensive cytogenetic and molecular testing to identify UHR MM patients.
• Employ multiparameter flow cytometry and imaging for sensitive MRD monitoring.
• Administer ILD regimen orally with scheduled dosing and monitor closely for toxicity.
• Discontinue therapy promptly if severe infection or organ toxicity occurs.
• Consider ILD maintenance therapy in relapsed/refractory UHR MM patients following CAR-T to optimize MRD eradication.

References

• China Cancer Foundation Project
• International Myeloma Working Group (IMWG) Response Criteria 2026
• mSMART 3.0 Risk Stratification System
• 2024 Revised Guidelines for Diagnosis and Treatment of Multiple Myeloma in China