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SDIRSACR Oncology Insights

induced immune suppression. Bispecific antibodies and CAR-T cells represent an innovative way to engage the immune
system within the TME by linking T cells directly to tumor cells, bypassing some of the suppressive signals.
The shift toward chemotherapy-free or reduced-intensity regimens involves combining targeted agents,
immunotherapies, and epigenetic drugs to deliver effective treatment with reduced toxicity. This translates into
fewer hospitalizations, less transfusion dependence, and improved quality of life. The reduction in treatment-related
morbidity and late toxicity is critical for long-term survivors, as many hematological malignancies occur in older adults
who are particularly vulnerable to the cumulative toxic effects of chemotherapy, including cardiotoxicity, neuropathy,
marrow suppression, and secondary malignancies.
Reducing the need for stem cell transplantation
Historically, ASCT has been a cornerstone in consolidating remission in MCL and MM. In relapsed and refractory cases,
ASCT has been the standard of care following salvage chemotherapy in chemosensitive NHL patients. While effective,
ASCT is associated with significant acute toxicities, prolonged hospitalizations, and long-term risks such as infertility,
secondary cancers, and organ dysfunction. The introduction of novel targeted agents and immunotherapies has
enabled many patients to achieve durable remissions without ASCT.
Allogeneic stem-cell transplantation (alloSCT) is rarely used in frontline settings but remains an option in selected
relapsed or high-risk cases, particularly in AL. Novel therapies are increasingly allowing some patients to delay or avoid
transplantation, thereby reducing morbidity and preserving patients’ quality of life, without compromising long-term
outcomes.
Conclusion
The benefits of combination therapies in hematological malignancies are profound and multifaceted. By harnessing
the synergistic effects of cytotoxic chemotherapy, targeted agents, immunotherapies including bispecific antibodies
and CAR T cells, and epigenetic drugs, guided by molecular profiling and an improved understanding of the tumor
microenvironment, clinicians can achieve deeper remissions, longer survival, and improved quality of life. As research
continues to unravel the molecular complexity of hematological malignancies and their interactions with the immune
system and TME, future combination therapies are expected to become increasingly personalized, precise, and effective.
These advances will not only improve response rates, survival, and quality of life, but also reduce treatment-related
toxicity and the need for intensive interventions such as transplantation or prolonged hospitalization. By achieving
deeper remissions with less morbidity, these approaches may prove to be more cost-effective, reducing the long-term
economic burden on healthcare systems.

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