Plasma Cell Neoplasm: Multiple Myeloma — Procedure Guide, Recovery & Risks | MyMedicPlus

Multiple myeloma is a malignancy of clonal plasma cells that accumulate in the bone marrow, produce a monoclonal immunoglobulin (M-protein), and cause end-organ damage characterised by the CRAB criteria: hyperCalcaemia, Renal impairment, Anaemia, and Bone lesions (osteolytic). It is the second most common haematological malignancy, with a median age at diagnosis of 65–70 years. The disease progresses from the precursor state of monoclonal gammopathy of undetermined significance (MGUS) through smouldering myeloma to symptomatic active myeloma requiring treatment. Modern therapy has transformed myeloma from a rapidly fatal disease into a chronic condition with median overall survival exceeding 5–7 years. Treatment is highly individualised, guided by cytogenetic risk stratification, age, performance status, and comorbidities, and centres on induction chemotherapy with proteasome inhibitor/immunomodulatory drug combinations, autologous stem cell transplantation (ASCT) in eligible patients, and maintenance therapy. Multiple myeloma is a malignant plasma cell neoplasm characterised by clonal proliferation of plasma cells in the bone marrow, producing monoclonal immunoglobulin (paraprotein — M-protein) detectable in serum and/or urine (Bence Jones protein). It accounts for approximately 10% of haematological malignancies and 1% of all cancers. Clinical manifestations follow the CRAB criteria: hyperCalcaemia, Renal impairment, Anaemia, and Bone disease (lytic lesions, vertebral fractures, osteoporosis). SLiM CRAB criteria expand this with serum free light chain ratio over 100, clonal bone marrow plasma cells over 60%, and MRI lesions. Treatment has been transformed by novel agents — proteasome inhibitors (bortezomib, carfilzomib, ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide), anti-CD38 monoclonal antibodies (daratumumab, isatuximab), and anti-BCMA therapies (belantamab mafodotin, teclistamab CAR-T). Despite being incurable with current therapy, median survival has extended from 3 years in the 1990s to over 8–10 years in transplant-eligible patients with modern combination regimens.

Active treatment is indicated for patients with symptomatic multiple myeloma meeting CRAB criteria or fulfilling biomarker criteria (bone marrow plasma cell percentage above 60%, serum free light chain ratio above 100, or more than one focal lesion on MRI). Smouldering myeloma with high-risk features may be treated in clinical trials. High-dose chemotherapy followed by ASCT is the standard of care for transplant-eligible patients (generally those under 70–75 years of age with adequate organ function), achieving deeper responses and longer progression-free survival than chemotherapy alone. Transplant-ineligible patients (older age, comorbidities) receive non-transplant induction regimens without high-dose conditioning. Cytogenetic risk assessment using FISH (fluorescence in situ hybridisation) identifies high-risk features — del(17p), t(4;14), t(14;16) — that inform treatment intensity and choice of regimen.

Treatment proceeds in sequential phases. Induction chemotherapy (typically 4–6 cycles) uses a triplet regimen such as bortezomib-lenalidomide-dexamethasone (VRd) or carfilzomib-lenalidomide-dexamethasone (KRd) to achieve maximal depth of response (minimal residual disease negativity is the optimal goal). Peripheral blood stem cells are then harvested by apheresis after granulocyte colony-stimulating factor (G-CSF) mobilisation. High-dose chemotherapy conditioning with melphalan (200 mg/m²) ablates the residual myeloma clone and the patient's immune system. The harvested autologous stem cells are infused to rescue the bone marrow, recovering neutrophil and platelet counts over 10–14 days. ASCT is followed by maintenance therapy with lenalidomide (10 mg daily continuously) or bortezomib-based regimens for 2 years or until progression, significantly prolonging progression-free survival. Daratumumab-based quadruplet induction and maintenance has been incorporated into leading protocols following MAIA and GRIFFIN trial results. Treatment is stratified by transplant eligibility (typically age under 70, adequate organ function). Transplant-eligible patients receive induction chemotherapy (VRd — bortezomib/lenalidomide/dexamethasone, or daratumumab-VRd), followed by peripheral blood stem cell collection, high-dose melphalan conditioning, and autologous stem cell transplant (ASCT). Post-transplant consolidation and lenalidomide maintenance therapy extend remission duration. Transplant-ineligible patients receive VRd or daratumumab-Rd as ongoing therapy. Bispecific antibodies (teclistamab — anti-BCMA x anti-CD3) and CAR-T cell therapy (ciltacabtagene autoleucel — cilta-cel; idecabtagene vicleucel — ide-cel) are approved for heavily pre-treated relapsed/refractory myeloma, achieving deep responses in patients who have exhausted conventional options.

Modern triplet induction regimens achieve overall response rates of 85–95%, with complete response or better in 40–60%. ASCT consolidation deepens response and prolongs median progression-free survival (PFS) to 50–60 months compared with 30–40 months without transplant. Five-year overall survival exceeds 50–60% in transplant-eligible patients with standard-risk cytogenetics treated with current protocols. Lenalidomide maintenance post-ASCT prolongs PFS by approximately 18 months. Daratumumab-based quadruplet regimens achieve minimal residual disease (MRD) negativity in 60–70% of patients — a deep response associated with superior long-term outcomes. For relapsed/refractory myeloma, chimeric antigen receptor (CAR) T-cell therapy (idecabtagene vicleucel, ciltacabtagene autoleucel) achieves response rates of 70–97% with deep and durable remissions in heavily pre-treated patients. Modern triplet or quadruplet induction regimens achieve complete response (CR) or very good partial response (VGPR) in 70–90% of newly diagnosed transplant-eligible patients. Daratumumab-based quadruplet induction (Dara-VRd) achieves MRD-negativity (measurable residual disease negativity by next-generation sequencing) in 50–60%, a key prognostic marker associated with prolonged progression-free survival. ASCT doubles progression-free survival compared to non-transplant strategies in eligible patients. Lenalidomide maintenance after transplant reduces relapse risk and extends PFS by 2–4 years. CAR-T and bispecific therapies provide meaningful response rates of 60–70% in multi-refractory disease where no other options exist.

Induction chemotherapy risks include bortezomib-related peripheral neuropathy (30–40%, often dose-limiting), dexamethasone-related hyperglycaemia, fluid retention and mood changes, infection from immunosuppression, and thromboembolic events (managed with aspirin or anticoagulation prophylaxis with lenalidomide). ASCT carries transplant-related mortality of under 2% at experienced centres but significant morbidity: febrile neutropenia during engraftment, mucositis (Grade 3–4 in 30–40%), and infectious complications (bacterial, viral, fungal). Renal impairment from myeloma itself or nephrotoxic drugs requires dose adjustment and supportive care. Bone disease causing vertebral fractures and cord compression requires bisphosphonate therapy (zoledronic acid monthly for 2 years) and orthopaedic or radiation oncology intervention. Secondary primary malignancies are a small but recognised long-term risk with lenalidomide maintenance. Myeloma therapy risks include myelosuppression (anaemia, neutropenia, thrombocytopenia), infection (pneumococcal vaccination and herpes zoster prophylaxis are essential), peripheral neuropathy (bortezomib — typically sensory; managed by dose reduction and subcutaneous administration), venous thromboembolism (lenalidomide plus dexamethasone — anticoagulation prophylaxis required), and renal toxicity. ASCT carries a transplant-related mortality of under 1% at specialist centres but requires 2–4 weeks of hospitalisation. Stem cell rescue for high-dose melphalan conditioning requires adequate stem cell collection. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are CAR-T specific toxicities managed in specialist centres.

After ASCT, patients remain hospitalised in a protective environment (HEPA-filtered room) for approximately 3–4 weeks until neutrophil engraftment (count above 0.5 × 10⁹/L) and platelet independence are achieved. Prophylactic antiviral (aciclovir against VZV reactivation), antifungal (fluconazole), and Pneumocystis jirovecii pneumonia (cotrimoxazole) prophylaxis are given through the immunosuppressed period. Full immune reconstitution takes 6–12 months post-ASCT. Fatigue is prominent for 3–6 months and is managed with graded exercise and psychological support. Maintenance therapy is administered as outpatient oral lenalidomide or subcutaneous bortezomib injections with regular haematological monitoring. Response assessment using serum M-protein, free light chains, and MRI/PET-CT is performed every 3 months. Disease progression is managed with sequential salvage regimens incorporating novel agents (pomalidomide, daratumumab, carfilzomib) and CAR-T therapy. Following ASCT, engraftment occurs at day 10–14 with gradual immune reconstitution over 3–12 months. Infection prophylaxis (antibacterial, antiviral, antifungal) is continued post-transplant. Disease monitoring uses serum protein electrophoresis, serum free light chains, and bone marrow biopsy with MRD assessment to guide maintenance therapy duration. Bone disease is managed with intravenous bisphosphonates (zoledronic acid monthly for 2 years) and surgical stabilisation for pathological fractures. Renal function monitoring guides lenalidomide dose adjustment. Quality of life assessment using EORTC QLQ-MY20 guides supportive care decisions throughout treatment.