Revolutionizing Blood Cancer Treatment:
A Dive into Cutting-Edge Therapies

The CAR-T Revolution: Transforming Treatment Paradigms

In the realm of blood cancer treatment, the introduction of chimeric antigen receptor T-cell (CAR-T) therapies represented a key paradigm shift. Since Novartis’ groundbreaking FDA approval of Kymriah for Acute Lymphoblastic Leukemia in 2017, the landscape has shifted dramatically. Now, with multiple CAR-T therapies securing FDA approval and thousands of patients treated, along with highly durable, long-term outcomes (upwards of 50% CR rate at 3 years for CD19 CAR-T across DLBCL, low-grade B-cell lymphoma, and CLL¹) the impact of these innovative treatments cannot be overstated.

CAR-T therapies have now expanded their reach across multiple cancers, including DLBCL, FL, MCL, and MM. Despite safety concerns raised by the FDA in 2023 regarding development of T-cell malignancies in patients who had received CAR-T², they have persevered and continue to gain traction. BMS’s Breyanzi received FDA approval in March 2024 for the treatment of CLL, with J&J’s Carvykti and BMS’ Abecma also moving into earlier-stage MM.

Beyond CAR-T: The Rise of Bispecifics

While CAR-T therapies have taken the spotlight, bispecific antibodies have emerged as compelling alternatives, offering additional avenues to combat recurrent disease. Though bispecifics may not yet match CAR-T efficacy levels (Tecvayli ORR of 63%³ vs 97%⁴ for Carvykti in 4L+ MM), they present an off-the-shelf alternative, devoid of the supply constraints that often plague CAR-T therapies, whilst offering comparable safety profiles. While CAR-T is likely to remain the first option where available, the greater accessibility and easier manufacturing of bispecifics will allow widespread use, particularly where access to CAR-T is limited.

Recent approvals for Roche’s CD20xCD3 bispecifics, Columvi and Lunsumio, alongside J&J’s Tecvayli & Talvey and Pfizer’s Elrexfio, further enrich the treatment arsenal for DLBCL, FL, and MM respectively. Additionally, therapies against novel targets such as J&J’s Talvey and Roche’s forimtamig, GPRC5DxCD3 bispecifics, may be used strategically with BCMA-targeting therapies for MM, signalling a promising direction for future treatments. While BCMA and GPRC5D bispecific combination therapies may prove unfeasible due to the risk of infections, alternating use line-on-line or utilising GPRC5D in patients with BCMA loss or intolerable AEs will provide additional hope for patients who have exhausted all current SoC therapies.

Navigating Uncertainties: Sequencing and Safety Concerns

However, amid these strides critical questions remain, particularly regarding the sequencing of both platforms and targets. As CAR-T and bispecifics advance into earlier lines of therapy, concerns arise regarding T-cell exhaustion and reduced efficacy in subsequent treatments. Furthermore, apprehensions surrounding secondary malignancies may impede frontline patient uptake with the FDA adding boxed warnings to all CD19 and BCMA targeting CAR-T therapies⁵.