Multiple Myeloma and BMT: Current Standards of Care

Multiple myeloma is a type of blood cancer that affects plasma cells, a vital part of the immune system. These cells are found in the bone marrow and are responsible for producing antibodies that fight infection. In multiple myeloma, abnormal plasma cells multiply uncontrollably and accumulate in the bone marrow, disrupting the production of healthy blood cells and leading to symptoms such as bone pain, fatigue, recurrent infections, and kidney problems. https://bmtnext.com/

Over the years, significant progress has been made in the management of multiple myeloma. Among the most important treatment options is Bone Marrow Transplant (BMT), more accurately termed Haematopoietic Stem Cell Transplant (HSCT). This procedure has become a cornerstone of care, especially for patients who are fit and have responded to initial therapy.

In this article, we will explore the role of BMT in multiple myeloma, covering the types of transplant, patient eligibility, procedure details, risks, recovery, and the latest advancements shaping the standard of care.

Understanding Bone Marrow Transplant in Multiple Myeloma

In the context of multiple myeloma, autologous stem cell transplant (ASCT) is the most commonly used form of bone marrow transplant. This involves using the patients own stem cells, which are collected, preserved, and later reinfused after high-dose chemotherapy. The goal of ASCT is not to cure the disease but to achieve a deeper and longer-lasting remission.

Allogeneic stem cell transplant (using donor stem cells) is rarely used in multiple myeloma due to a higher risk of complications, such as graft-versus-host disease (GVHD), and limited evidence of better long-term outcomes compared to autologous transplant. However, it may be considered in younger patients with high-risk disease or relapse after autologous transplant.

Who is eligible for BMT?

Not all patients with multiple myeloma are eligible for a bone marrow transplant. Eligibility is generally based on:

• Age: Most centres offer ASCT to patients up to 6570 years of age, depending on overall health.

• Performance Status: The patient must be physically fit to handle the transplant and its side effects.

• Organ Function: Adequate heart, lung, liver, and kidney function are critical.

• Disease Response: A good response to initial chemotherapy (induction therapy) improves transplant outcomes.

Patients with aggressive disease, multiple comorbidities, or poor functional status may be better managed with novel therapies rather than transplant.

The Transplant Process: Step-by-Step

1. Induction Therapy

Before transplant, patients receive 34 cycles of combination chemotherapy. Regimens such as VRd (bortezomib, lenalidomide, dexamethasone) or KRd (carfilzomib, lenalidomide, dexamethasone) are commonly used to reduce tumour burden.

2. Stem Cell Collection

After induction therapy, the patients stem cells are mobilised from the bone marrow into the bloodstream using growth factors (like G-CSF) and sometimes with chemotherapy. These cells are then collected through a process called apheresis and frozen for later use.

3. Conditioning Regimen

Patients receive high-dose chemotherapy, usually melphalan, to destroy remaining cancerous cells in the bone marrow. While effective, this chemotherapy wipes out the bone marrows ability to make new blood cellshence the need for stem cell rescue.

4. Stem Cell Infusion

The previously collected stem cells are thawed and infused intravenously. These cells migrate to the bone marrow and start producing new, healthy blood cells over the next 23 weeks.

5. Engraftment and Recovery

Patients are monitored for engraftment, which is when the new stem cells begin producing white cells, red cells, and platelets. During this time, patients are at high risk of infection and bleeding and are closely watched in a transplant unit or outpatient setting.

Benefits of BMT in Multiple Myeloma

Autologous transplant offers several benefits:

• Deeper Remission: ASCT helps achieve minimal residual disease (MRD) negativity, associated with longer progression-free survival.

• Improved Survival: While not curative, ASCT extends both progression-free and overall survival compared to chemotherapy alone.

• Long-Term Disease Control: Patients can enjoy years of remission post-transplant, especially when combined with maintenance therapy.

Risks and Complications

While generally safe, ASCT carries potential risks:

• Infections: The immune system is severely weakened during the procedure.

• Mucositis: Painful inflammation of the mouth and digestive tract due to chemotherapy.

• Fatigue: Can last for weeks to months post-transplant.

• Gastrointestinal issues: Nausea, diarrhoea, and loss of appetite are common.

• Relapse: Multiple myeloma almost always recurs, requiring further treatment.

Allogeneic transplant has additional risks, including graft-versus-host disease, and is reserved for specific cases.

Maintenance Therapy After BMT

Post-transplant, most patients receive maintenance therapy, commonly with lenalidomide, to prolong remission. Maintenance has been shown to:

• Increase progression-free survival.

• Delay relapse.

• Possibly improve overall survival, especially in standard-risk patients.

Treatment is typically continued until disease progression or intolerable side effects.

Recent Advances and Innovations

Several developments are reshaping the standard of care in multiple myeloma:

1. MRD Testing

Minimal Residual Disease testing allows doctors to measure how deeply the cancer has responded. MRD-negative status is associated with better outcomes and may guide post-transplant decisions.

2. Tandem Transplant

Some high-risk patients may benefit from two consecutive ASCTs, known as tandem transplants, especially in younger individuals or those with suboptimal responses to the first.

3. CAR-T Cell Therapy

While not yet replacing transplant, CAR-T therapy (like idecabtagene vicleucel and ciltacabtagene autoleucel) offers promising results in relapsed/refractory cases.

4. Bispecific Antibodies

Agents like teclistamab target both myeloma cells and T-cells, enhancing immune attack and potentially reducing relapse risk after transplant.

Conclusion

Bone marrow transplant remains a cornerstone in the treatment of eligible multiple myeloma patients. With improvements in transplant techniques, supportive care, and post-transplant therapies, outcomes have significantly improved over the past two decades.

While not curative, ASCT provides a path to deeper remissions, longer survival, and better quality of life. The integration of BMT with newer treatment options such as maintenance therapies, immunotherapy, and precision medicine continues to raise the standard of care in multiple myeloma.

For patients and carers, understanding the transplant journeyits challenges, benefits, and long-term managementis essential in making informed treatment decisions and maintaining hope for a better future.https://bmtnext.com/