Multiple Myeloma

Myeloma is characterised by clonal proliferation of plasma cells in the bone marrow, which infiltrate organs like kidneys and the bones causing kidney failure, bone destruction, increase in calcium and compromised bone marrow function causing anemia.

This starts with a rather benign but a clonal condition where a single clone of plasma cells (cells producing antibodies to fight infections) slowly expand over years. This condition is called Monoclonal Gammopathy of uncertain significance (MGUS). It takes on an average a decade or two for 50% of those with MGUS to progress to Myeloma. Myeloma stays asymptomatic or indolent initially (Indolent Myeloma), before it takes a more aggressive form.

Before the recent advancements in understanding and management of myeloma, median survival was only 3 years.

Most commonly, MGUS is an incidental finding, suspected when the globulin fraction of the protein is high in the absence of infections or liver disease. The same is true for Indolent Myeloma. MGUS is differentiated from Indolent Myeloma based on the number of clonal plasma cells in the marrow (>10% to call it a Myeloma).

In symptomatic myeloma, the affected person can present with any of the following:

• Bone pain — particularly low back pain
• Kidney failure
• Increased excretion of protein in the urine causing the body to swell up. This is often associated with deposition of abnormal proteins in kidneys and other parts of the body. This condition is called AL Amyloidosis.
• Increased calcium in blood resulting in confusion, constipation, nausea and abnormal heart rhythm.
• Anemia

The initial diagnosis of myeloma is made based on a set of investigations:

• Serum protein electrophoresis and immunofixation
• Serum free light chain assay
• Bone marrow Examination
• Cytogenetics and molecular studies
• Added investigations — B2-microglobulin / LDH / Albumin
• PET-CT of the entire skeletal system and the whole body to assess the extent of bone involvement and any extramedullary involvement (other than bone and bone marrow)

Confirmation of clonality of plasma cells is made by Immunophenotyping with multicolour Flow Cytometry and Immunohistochemistry on biopsy sample.

The current prognostic scoring system for myeloma (IPS-R) incorporates simple blood tests like albumin, B2-microglobulin and LDH along with cytogenetic findings. Based on this scoring system, three risk stratifications are created — low, intermediate and high.

Indolent Myeloma

Indolent myeloma is an asymptomatic condition and traditionally has not been treated. However, the current trend is to treat such patients so that the chances of myeloma related complications are reduced.

First-line therapy

A combination of Bortezomib, lenalidomide and dexamethasone with or without Daratumumab is the current first line treatment. Most patients show encouraging response to this treatment.

In those less than 65 years and those between 65-70 years with good fitness should go on to receive an Autologous HCT. This should be followed by a maintenance therapy with lenalidomide for 2 years. 70% of low or intermediate patients remain disease-free at 5 years with this approach.

Relapsed Disease

In patients with early relapse, a bispecific T cell engager such as Teclistamab or Elranatamab should be chosen in combination with Daratumumab or alone.

CAR-T cell Therapy directed at BCMA is also an option for relapsed/refractory Myeloma.

Finally, the only proven curative therapy for myeloma is an Allogeneic HCT. If used judiciously and early it can cure a substantial number of patients with early relapse.