What is the initial treatment for a patient with T(11,14) multiple myeloma?

Initial Treatment for T(11;14) Multiple Myeloma

For patients with t(11;14) multiple myeloma, standard triplet induction therapy with bortezomib, lenalidomide, and dexamethasone (VRd) remains the preferred initial treatment, with the critical caveat that venetoclax-based regimens should be reserved for relapsed/refractory disease rather than upfront therapy. 1, 2

Induction Therapy Approach

Transplant-Eligible Patients

• VRd (bortezomib, lenalidomide, dexamethasone) is the preferred induction regimen, achieving 58% VGPR or better rates and 52% complete response rates 2
• Administer for approximately 4 cycles prior to stem cell collection 2, 3
• Bortezomib should be given subcutaneously rather than intravenously to significantly reduce peripheral neuropathy risk 2, 4
• Weekly bortezomib dosing is preferred over twice-weekly to minimize neuropathy while maintaining efficacy 2
• Following induction, proceed to high-dose melphalan (200 mg/m²) with autologous stem cell transplantation using peripheral blood progenitor cells 2, 3

Transplant-Ineligible Patients

• VRd remains the preferred triplet regimen with dose modifications for elderly patients 4
• Reduce dexamethasone to 20 mg weekly for patients >75 years, with further reduction to 8-20 mg weekly for frail patients 4
• Continue therapy until progression rather than fixed-duration treatment, as continuous therapy improves both progression-free and overall survival 4

Critical Distinction: T(11;14) Is NOT High-Risk

T(11;14) is classified as standard-risk cytogenetics, not high-risk 1. The International Myeloma Working Group consensus defines high-risk as del(17p), t(4;14), and t(14;16), with t(11;14) specifically included in an extended panel but not categorized as adverse 1. This distinction is crucial because:

• Standard VRd induction is appropriate; there is no need for intensified bortezomib-based therapy required for true high-risk disease 2, 3
• Lenalidomide maintenance (rather than bortezomib-based maintenance) is suitable after transplant 2, 3

Maintenance Therapy

• Lenalidomide maintenance should be continued until progression after autologous transplant, providing median progression-free survival of 41 months 4, 3
• For standard-risk patients including t(11;14), lenalidomide maintenance is preferred over bortezomib-based maintenance 2, 3

Venetoclax: Reserved for Relapse

Venetoclax-based therapy is specifically indicated for relapsed/refractory t(11;14) myeloma, not initial treatment 1. The evidence shows:

• Venetoclax/dexamethasone with or without daratumumab or a proteasome inhibitor is included as an option for patients with t(11;14) translocation in the relapsed setting 1
• In relapsed/refractory patients with t(11;14), venetoclax/dexamethasone achieved 48% overall response rate with median time to progression of 10.8 months 1
• Venetoclax monotherapy showed 40% response rate in t(11;14) patients versus only 6% in those without this translocation 1
• Adding daratumumab or proteasome inhibitors to venetoclax/dexamethasone produces high rates of durable responses in relapsed t(11;14) disease 1

Essential Supportive Care

• Thromboprophylaxis is mandatory for all patients receiving lenalidomide-based therapy 2, 4, 3
• Herpes zoster prophylaxis should be administered 4
• Bisphosphonates should be given to reduce skeletal-related events 3

Response Monitoring

• Assess response with each treatment cycle using serum and urine protein electrophoresis and serum free light chains 4, 3
• Complete response requires <5% plasma cells in bone marrow and negative immunofixation 3
• Whole-body low-dose CT is preferred over conventional skeletal survey for bone assessment 2, 3

Common Pitfall to Avoid

Do not use venetoclax as initial therapy for t(11;14) myeloma. While t(11;14) confers venetoclax sensitivity due to BCL-2 overexpression, all guideline evidence positions venetoclax-based regimens exclusively in the relapsed/refractory setting 1. Standard VRd induction followed by transplant (if eligible) and lenalidomide maintenance remains the evidence-based approach for newly diagnosed disease 2, 4, 3.