In the Cartitude 1 trial, the strongest predictor of long-term remission with Siltacel was a lower burden of disease (measured by bone marrow percentage and soluble BCMA levels), rather than the number of prior treatments. This implies using CAR-T therapy earlier in the disease course is more effective.

The treatment backbone for Ph+ ALL is shifting away from intensive chemotherapy like hyper-CVAD. Chemotherapy-free regimens combining blinatumomab with a TKI (preferably ponatinib) are becoming the new standard, showing outcomes that are at least as good as, and likely better than, traditional chemotherapy.

In follicular lymphoma, the treatment goal is durable remission with manageable toxicity, not necessarily a cure. Therefore, clinicians frequently prefer using a bispecific antibody first, reserving the more complex and toxic CAR-T cell therapy for transformed disease or after a bispecific fails.

Unlike some targeted therapies that lead to antigen loss, treatment with the CD19-directed antibody tafasitamab does not appear to eliminate CD19 expression on lymphoma cells. This is a critical finding, as it preserves the target for subsequent potent therapies like CD19-directed CAR T-cells.

BTK inhibitors like ibrutinib can improve T-cell function. When combined with liso-cel CAR-T, this synergistic effect dramatically improves outcomes in heavily pretreated patients, increasing the complete response rate from 20% to 45% and the overall response rate from 48% to 86%.

As CAR-T cell therapies are increasingly adopted for second-line treatment of large cell lymphoma, epcoritamab is solidifying its role as a critical, potentially curative replacement option in the third-line setting. This establishes a clear sequential treatment pathway for patients who continue to relapse.

Using a BCMA bispecific antibody first can exhaust a patient's T-cells or cause tumors to lose the BCMA target, rendering a subsequent BCMA-targeted CAR-T therapy ineffective. The optimal sequence is CAR-T first, which preserves T-cell function and BCMA expression, leaving bispecifics as a viable later-line option.

Contrary to typical findings where real-world data underperforms, liso-cel CAR T-cell therapy in CLL demonstrates significantly better outcomes in practice than in its approval trial (over 80% response rate vs. under 50%). This suggests that using the therapy earlier in healthier, less-refractory patients unlocks its true potential.

Before initiating a CD20-targeting bispecific antibody in patients who have failed CAR-T therapy, a new biopsy is mandatory. Up to 30% of these patients experience CD20 antigen loss, which would render the bispecific therapy ineffective and necessitates choosing a drug with a different target.