February 2015, Vol 4, No 1
Case Report: Intense Maintenance in a Woman with High-Risk Multiple Myeloma
Tremendous progress has been made in the treatment of patients with multiple myeloma (MM) over the past 2 decades. The 5-year relative survival ratio increased from 26.3% in 1975 to 45.1% in 2006, when only 3 drugs were approved for the treatment of MM. The arsenal of drugs approved by the FDA has now expanded to include thalidomide, lenalidomide, bortezomib, doxorubicin, carfilzomib, and pomalidomide.
â€śWe have more treatment options, leading to more [treatment] heterogeneity,â€ť said Ajay K. Nooka, MD, MPH, assistant professor of hematology and medical oncology, Winship Cancer Institute of Emory University, Atlanta, GA. â€śThere is no consensus amongst us about what is optimal induction therapy and optimal salvage therapies.â€ť
Although several molecular biomarkers are under development, genetic biomarkers are more acceptable for guiding therapy in MM. Chromosomal abnormalities in MM are translocations involving 14q32: t(11;14), t(4;14), and t(14;16); chromosome 13 abnormalities: monosomy, del(13), 13q translocations; del(17p); and hyperdiploidy.
High-risk features include the presence or deletion of p53; deletion of 1p; immunoglobulin heavy chain translocations â€“ t(4;14) or t(14;16) â€“ by fluorescence in situ hybridization (FISH) or by metaphase cytogenetics; or presentation as plasma cell leukemia (?20% circulating plasma cells in peripheral blood).
A case report in high-risk MM was presented by Nooka at the Third Annual PMO Live Conference, a Global Biomarkers Consortium Initiative.
Case: Stage III MM
A 57-year-old Caucasian female diagnosed with stage III MM in October 2008 presents with back pain, fatigue, increasing shortness of breath, chest pain, and progressive anemia for 1 year. Her presenting laboratory values are as follows: total protein, 7.4 g/dL; protein, 2.1 g/dL (IgG kappa); ?2-microglobulin, 19.9; free kappa, 1407 mg/L; free lambda, 9 mg/L; ratio, 145; IgG, 3195 mg/dL; IgA, <40 mg/dL; IgM, <35 mg/dL; hemoglobin, 5.4; hematocrit, 16; platelet count, 241; creatinine, 1.8 mg/dL; calcium, 9.2 mg/dL.
A bone marrow biopsy showed 90% cellularity with 22% plasma cells. FISH revealed del(17p) in 43 of the 50 cells.
An MRI of the spine revealed a compression fracture at L5. The patient underwent kyphoplasty and then initiated induction therapy with lenalidomide, bortezomib, and dexamethasone (RVD).
Although improvements in progression-free survival (PFS) and overall survival (OS) have been realized across all stratifications of patients with MM, progress has been less impressive among high-risk patients with del(17p), said Nooka. These patients have a PFS of close to 1 year and a median OS of 18 to 24 months.
The case patient is young with a high tumor burden and is transplant eligible, and the consensus is to treat with a combination of immunomodulatory therapy and proteasome inhibitor therapy. Obtaining a response with bortezomib-containing induction regimens is relatively easy, said Nooka, but the challenge is to maintain a response among high-risk patients such as this one.
After induction with 4 cycles of RVD, a stringent complete response (sCR) is obtained in nearly 20%. After autologous stem cell transplant, the rate of CR plus sCR improves to about 40%. A consolidation/maintenance approach to treatment to continuously suppress malignant clones has been evaluated in high-risk patients with MM. With initiation of RVD maintenance, 51% of patients achieved sCR, and 96% achieved at least a very good/partial response as best response (Leukemia. 2014;28:690-693). The RVD maintenance regimen translated into a median PFS of 30 months and a 3-year OS of 93% in patients with del(17p). The regimen was well tolerated with no grade 3/4 neuropathy.
â€śIf weâ€™re able to give an initial induction therapy with a combination of a proteasome inhibitor, an immunomodulatory drug, and steroids, give it early after transplant, and maintain the response with a maintenance regimen consisting of those 3 agents, we are able to deliver good response rates, and the safety is acceptable,â€ť he said. â€śWeâ€™ve never had a patient who was not able to tolerate this maintenance regimen.â€ť
He continued, â€śI would treat this patient with initial induction therapy with RVD for 4 cycles, early transplant, and an intense maintenance approach.â€ť
The question then becomes: how long should the intense maintenance approach be continued? In the case patient, intense maintenance was continued for 3 years, followed by single-agent lenalidomide maintenance. The patient continues to do well.
While on RVD maintenance (and single-agent lenalidomide), continuation of bisphosphonates, thromboprophylaxis, and prophylactic acyclovir is advised.
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