Following multidisciplinary consultation, the patient was treated with the bendamustine plus rituximab (BR) regimen. Second, for WM patients with renal AL amyloidosis, choosing BR regimen as the first-line treatment is reasonable. However, during the treatment process, it is essential to closely monitor and actively prevent the adverse effects of this regimen, particularly severe infections which may have fatal consequences.

P2, N=39, Recruiting, University of Maryland, Baltimore | Trial completion date: Feb 2027 --> Feb 2028 | Trial primary completion date: Jun 2026 --> Jun 2027

P1, N=156, Recruiting, Kyowa Kirin Co., Ltd. | N=72 --> 156 | Trial completion date: Apr 2028 --> Nov 2031 | Trial primary completion date: Dec 2026 --> Nov 2031

P2, N=24, Recruiting, University of California, Davis | Trial primary completion date: Feb 2026 --> Oct 2026

Three cases (8%) of non-fatal sinusoidal obstructive syndrome (SOS) were observed. Inotuzumab was safe and effective at eradicating MRD.

We discuss the biological rationale for combination approaches and summarize the key clinical studies that have defined current practice, including trials evaluating FLT3 inhibitors, gemtuzumab ozogamicin, IDH inhibitors, and venetoclax-based strategies. While genotype-directed strategies-such as FLT3 inhibition-have already demonstrated survival benefit, optimal patient selection, treatment sequencing, and duration remain areas of active investigation. Future progress will likely depend on MRD-driven treatment adaptation, improved understanding of clonal evolution, and the development of rational multi-agent combinations capable of achieving deeper and more durable remissions.

P1, N=7, Terminated, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | N=36 --> 7 | Trial completion date: Dec 2028 --> Jul 2025 | Active, not recruiting --> Terminated; Upon analysis of the first 7 participants accrued, it was determined that this combination treatment is not efficacious as treatment for patients with relapsed or refractory AML

Lastly, enhanced in vivo antitumor activity of vobramitamab duocarmazine by systemic A-1331852 was shown. Collectively, our findings provide rationale for the development of ADC therapies combining genotoxic payloads with BCL-XL inhibitors for mCRPC.

These findings identify time-limited p38 inhibition as a mechanism-based strategy to enhance INO-induced DNA cleavage and mitochondrial priming, resulting in markedly improved therapeutic efficacy in a very high-risk leukemia model. This work may provide a rationale for optimizing ADCbased combination therapies through transient inhibition of p38.

P2, N=9, Active, not recruiting, Georgetown University | Trial completion date: May 2026 --> Apr 2027

Human carbonic anhydrase IX (hCA IX) is markedly overexpressed in clear cell renal cell carcinoma and plays a key role in establishing an acidic tumor microenvironment associated with intrinsic chemoresistance. The resulting compounds were evaluated against hCA I, II, IX, and XII, displaying preferential inhibition of the tumor-associated isoforms. Selected derivatives (13a and 14c) showed antiproliferative activity in 786-O and CAKI-1 cells, inducing cell-cycle arrest and reducing long-term proliferative capacity more effectively than the reference CA IX inhibitor SLC-0111.

While fludarabine and cyclophosphamide (Flu/Cy) remain the standard LD regimen, bendamustine has emerged as a potential alternative due to its distinct immunomodulatory properties and more favorable toxicity profile. However, the current evidence is largely derived from retrospective and non-randomized studies. Prospective, comparative trials are warranted to validate these findings and to better define the optimal LD strategy across disease types and CAR-T platforms.