Clinical trials

The treatment options for multiple myeloma have evolved significantly over the years, providing patients with a range of therapies tailored to their specific circumstances. The choice of treatment often hinges on various factors, including the aggressiveness of the disease, individual prognostic indicators like genetic markers, the overall physical condition of the patient, and any pre-existing health issues that may affect treatment decisions. Current therapeutic strategies include several classes of drugs, each working through different mechanisms. Proteasome inhibitors (PIs) disrupt the protein degradation process within myeloma cells, thereby promoting their death. Immunomodulatory drugs (IMiDs) modulate the immune system and inhibit tumor growth by enhancing the body's natural anti-cancer responses. Monoclonal antibodies specifically target cancer cells, marking them for destruction by the immune system. In cases where patients are eligible, autologous stem cell transplantation remains a viable option, offering the potential for long-term remission by replacing damaged bone marrow with healthy stem cells from the patient's own body. Despite these advancements, multiple myeloma continues to present significant challenges, as it often recurs even after initial successful treatment and remains an incurable disease. This highlights the urgent need for innovative therapeutic strategies that can effectively address resistance to existing treatments, ultimately aiming to improve patient outcomes and survival rates.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children and the second most frequent acute leukemia in adults. B-cell ALL constitutes approximately 85% of all ALL diagnoses. In Pakistan, ALL represents the most prevalent haematological malignancy presenting to tertiary centres, with AFBMTC receiving the largest national referral volume for haematological malignancies and transplantation. First-line combination chemotherapy achieves complete remission (CR) in \>95% of paediatric patients; however, 15-20% relapse. Outcomes following first relapse are substantially inferior: second-line salvage chemotherapy achieves CR2 in 30-50% of patients, and long-term event-free survival (EFS) after conventional chemotherapy alone is \<10%. Outcomes in adult ALL are even more dismal, with OS at 5 years below 40% even in first CR without allogeneic transplant. Patients with primary refractory ALL or multiply relapsed ALL have an unmet medical need for novel therapeutic approaches. The classical paradigm of chemotherapy followed by allogeneic haematopoietic stem cell transplantation (allo-HSCT) is limited by donor availability, conditioning-related mortality, and inability to achieve remission before transplant.