Tag: Multiple Myeloma

SUMMARY: In this provocative perspective, the authors suggest revising the present Multiple Myeloma (MM) International Staging System, to incorporate more relevant information related to the biology of the disease. The MM International Staging System (MM-ISS) takes into account Beta-2 Microglobulin (B2M) along with Serum Albumin (SA) levels to determine the prognosis in MM patients. Although B2M and SA may act as surrogates for the extent of the disease, the evidence is insufficient to rely on these two entities to prognosticate MM. Even though B2M can correlate with MM tumor bulk as well as act as a biomarker of renal failure related to MM, the authors cite multiple studies suggesting that elevated serum B2M can be seen independent of MM history, in healthy elderly patients, infections, autoimmune disorders and chronic renal insufficiency. Further elevated B2M can be a marker of frailty in elderly patients and can predict disability and mortality in this patient group. With regards to Serum Albumin (SA) in MM, SA is inhibited by IL6, a MM cell growth factor and thus is able to indirectly reflect MM tumor bulk. However, low SA levels can also be seen in frail and elderly patients independent of MM history. The authors point out that the stage of the disease in the MM-ISS increases with age, independent of MM tumor bulk, due to the these nonspecific factors and does not necessarily correlate with other more specific prognostic markers such as cytogenetics, particularly in elderly patients. The authors conclude that combining the MM-ISS with tumor cytogenetics will more accurately predict prognosis in MM patients. Bataille R, Annweiler C, Beauchet O. Clinical Lymphoma Myeloma and Leukemia 2013;13:635-637

The authors in this provocative report recommend combining the Multiple Myeloma International Staging System (MM-ISS) with tumor cytogenetics, to more accurately predict prognosis in MM patients. The MM International Staging System (MM-ISS) takes into account a combination of Beta-2 Microglobulin (B2M) along with serum albumin (SA) levels to determine the prognosis in MM patients. Unfortunately both B2M and SA can be abnormal in elderly patients independent of Myeloma history and may predict disability and mortality in this patient group. The MM-ISS may therefore not accurately reflect the intrinsic malignancy of the myeloma cell clone. This information was published in Clinical Lymphoma Myeloma and Leukemia 2013. Read more at www.oncoprescribe.com

SUMMARY: Pomalidomide (POMALYST®) is a novel, oral, immunomodulatory agent which is far more potent than Thalidomide (THALOMID®) and Lenalidomide (REVLIMID®). Only 2% of POMALYST® is excreted unchanged through the kidney whereas 80% of REVLIMID® is excreted unchanged via the kidneys. Therefore, POMALYST® may be a consideration for patients with renal insufficiency. Previously conducted phase II trials have shown POMALYST® to be active in Myeloma patients, refractory to REVLIMID® and Bortezomib (VELCADE®). In a multicenter, randomized, phase III trial, the efficacy and safety of POMALYST® given along with low-dose Dexamethasone (LoDEX) (n=302) was compared with high-dose Dexamethasone (HiDEX) (n=153) in Myeloma patients, who were refractory to both REVLIMID® and VELCADE®. The primary endpoint was Progression Free Survival (PFS). The Overall Survival (OS) was only evaluated if PFS was statistically significant. With a median follow up of 10 months, the PFS was significantly longer in the POMALYST® + LoDEX group compared to the HiDEX group (4 month vs 1.9 months; hazard ratio [HR]= 0.48; P <0 .0001). The median OS was significantly longer in the POMALYST® + LoDEX group compared to HiDEX group (12.7 months vs 8.1 months; HR=0.74; P=0.028). The authors concluded that POMALYST® along with low- dose Dexamethasone should be the new standard of care for patients who have Multiple Myeloma refractory to REVLIMID® and VELCADE®. Carfilzomib (KYPROLIS®), a new parenteral proteasome inhibitor is another option for patients with resistant and refractory Multiple Myeloma. San Miguel J, Weisel K, Moreau P, et al. Lancet Oncol 2013;14:1055-1066

SUMMARY: Multiple Myeloma (MM) is a clonal disorder of plasma cells in the bone marrow. It evolves from a precursor stage called Monoclonal Gammopathy of Unknown Significance (MGUS) to MM. Smoldering Multiple Myeloma (SMM) is an intermediate stage in this process of disease evolution. The risk of MGUS transforming into MM is approximately 1% per year. SMM or asymptomatic MM is a precursor to MM and is characterized by at least 10% plasma cells in the bone marrow or a M-spike of at least 3 g/dl, or both, but these patients have no evidence of active symptomatic Myeloma with associated end-organ damage such as hypercalcemia, renal insufficiency, anemia or bone lesions. Even though only 10% of patients with SMM progress to MM annually, over 50% of the SMM patients with high risk features will progress to MM in the first 2 years. The current recommendations for those with SMM are periodic monitoring and treatment intervention only when disease progresses to MM. SMM patients with high risk features include those with at least 10% plasma cells in the bone marrow, a Monoclonal component (IgG monoclonal spike of at least 3g/dL, IgA M-spike of at least 2g/dL or a urinary Bence Jones protein level of more than 1g per 24 hours) or only one of the above two criteria plus at least 95% abnormal plasma cells in the bone marrow, with a reciprocal decrease in one or two uninvolved immunoglobulins of more than 25%, compared to normal values. Identifying those who are at a high risk for progression in the SMM group, is becoming more relevant with the availability of new promising therapies. In a phase III study, 119 patients with high risk SMM were randomly assigned to receive treatment (n=57) or to be observed until progression (n=62).Treatment consisted of Lenalidomide (REVLIMID®) 25 mg given on D1-D21 and Dexamethasone (DECADRON®) 20 mg given on D1-D4 and D12-D15 of a 4 week cycle. Patients received 9 cycles of therapy followed by maintenance therapy with REVLIMID® 10 mg given on D1-D21 every four weeks for 2 years. The median follow-up time was 40 months. The primary end point was time to progression to symptomatic disease. Secondary end points included response rate, overall survival, and safety. The median time to progression was significantly longer in the treatment group compared to the observation group (hazard ratio [HR] = 0.18; P< .001). At 3 years, the survival rate was better in the treatment group than in the observation group (94% vs 80% with a 69% reduction in the risk of death. P =0.03). Treatment related toxicities were grade 2 or lower. The authors concluded that treatment intervention for patients with high risk SMM may be of value, by delaying progression to symptomatic MM and extending overall survival. It remains to be seen if treatment intervention for patients with SMM will become the standard of care. It may also be relevant to include cytogenetics in the SMM definition criteria, as treatment intervention for SMM becomes an acceptable practice. Mateos M-V, Hernandez M-T, Giraldo P, et al. N Engl J Med 2013;369:438-447

Lambrolizumab (MK-3475) is a humanized anti–PD-1 monoclonal antibody that has demonstrated significant benefit for those patients with advanced Malignant Melanoma regardless of their prior therapy with anti-CTLA 4 antibody, YERVOY&reg; (Ipilimumab). The programmed death 1 (PD-1) receptor is an inhibitory receptor expressed on activated T-cells in the tumor micro environment. The anti–PD-1 antibody by blocking the PD-1 receptor essentially unleashes the immune system to fight off cancer cells. This information published in the NEJM in June 2013 and presented at the 2013 ASCO annual meeting gives an additional option for patients with advanced Malignant Melanoma.

Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) developed by the Mayo Clinic, unlike the present staging systems takes cytogenetic features into consideration and stratifies patients into High risk, Intermediate risk and Low risk groups. The clinician, based on the risk, then decides on the most appropriate therapy. This Risk-Adapted Therapy should result in better outcomes without compromising care. The 2013 mSMART Consensus Guidelines were published in the April issue of the Mayo Clinic Proceedings.