Citations

Despite successful treatment of the clonal plasma cell implicated in its pathogenesis, patients with AL amyloidosis (AL) experience significant morbidity related to underlying amyloid mediated organ dysfunction. While normalization of the serum free light chain measurements [normal ratio of involved and uninvolved free light chains (nFLCr)] is the goal of therapy and centerpiece of hematologic response criteria, achieving (or not achieving) meaningful organ response (OR) is clinically significant for its implications on long‐term symptomatology as well as overall survival (OS), and remains the ultimate goal of treatment. Expectations for organ recovery following successful therapy leading to nFLCr in AL remain poorly described. We evaluated the timeframe and predictive factors for OR, and long‐term outcome, in 313 AL patients who achieved nFLCr following therapy initiation. OR was seen in 80% of surviving AL patients within 1‐year of nFLCr. Patients achieving early OR within 1 year of nFLCr had superior OS compared with those who despite obtaining nFLCr did not achieve early OR. We further evaluated factors predicting OR and OS among patients achieving nFLCr. Higher values of dFLC (involved–uninvolved) at diagnosis predict OR, and early OR predicts improved OS following successful hematologic therapy in AL. Am. J. Hematol. 90:181–186, 2015. © 2014 Wiley Periodicals, Inc.

Summary The presence of clonal circulating plasma cells (c PC s) remains a marker of high‐risk disease in newly diagnosed multiple myeloma (MM) patients. However, its prognostic utility in MM patients with previously treated disease is unknown. We studied 647 consecutive patients with previously treated MM seen at the Mayo Clinic, Rochester who had their peripheral blood evaluated for c PC s by multi‐parameter flow cytometry. Of these patients, 145 had actively relapsing disease while the remaining 502 had disease that was in a plateau and included 68 patients in complete remission (CR) and 434 patients with stable disease. Patients with actively relapsing disease were more likely to have clonal c PC s than those in a plateau ( P < 0·001). None of the patients in CR had any clonal c PC s detected. Among patients whose disease was in a plateau, the presence of clonal c PC s predicted for a worse median survival (22 months vs. not reached; P = 0·004). Among actively relapsing patients, the presence of ≥100 c PC s predicted for a worse survival after flow cytometry analysis (12 months vs. 33 months; P < 0·001). Future studies are needed to determine the role of these findings in developing a risk‐adapted treatment approach in MM patients with actively relapsing disease.

Key Points Survival of patients with primary plasma cell leukemia has improved in recent years, but is still inferior to those patients with multiple myeloma. This survival benefit appears to be mainly in patients older than 65 years of age.

AbstractImmunoglobulin light chain (AL) Amyloidosis is a condition whereby misfolded proteins generated by plasma cells deposit in tissues causing organ dysfunction. Chemotherapy and autologous stem cell transplant when eligible are standard treatment options. Several studies report long‐term outcomes of patients post‐transplant. However, there is a paucity of literature describing outcomes of relapsed patients post‐transplant. We performed a retrospective study to assess outcomes and therapies employed upon relapse after transplant. Between 1996 and 2009, 410 patients received transplant at the Mayo Clinic as first‐line therapy. Of those patients, 42 (10%) died within 3 months of transplant, 64 (16%) died without documented relapse, 158 (38%) were alive without documented progression, and 146 (36%) had documented progression. Those 146 patients are the subject of our study, and their median time to hematologic relapse/progression was 23.6 months (95%CI 18.3, 26.3 months). Their median overall survival and 5‐yrs overall survival from post‐transplant relapse/progression was 51.7 months (95%CI 34.1–62.3) and 39%, respectively. The most common first regimen for treatment after relapse was lenalidomide or thalidomide. In conclusion, our study indicates that patients with AL amyloidosis fare well post‐transplant relapse/progression. Additionally, it provides a yardstick to design clinical trials to determine best treatment options.

There are no systematic data regarding nonmaintained induction for those patients with multiple myeloma (MM) who do not receive consolidative autologous stem cell transplantation. Of 173 patients with newly diagnosed MM treated with lenalidomide and dexamethasone (LenDex) as primary therapy, 31 patients had their lenalidomide discontinued for reasons other than progression or alternate therapy. Median progression free survival (PFS) from the time of discontinuing lenalidomide was longer in patients who received lenalidomide ≥1 year (39 vs. 13 months, P < 0.05); there was no difference in PFS for those treated for 1–2 years as compared to ≥2 years. Among those taking lenalidomide for ≥1 year PFS was superior in patients who were in very good partial response (VGPR) or better as compared to those with partial response (48.4 versus 14.8 months, P < 0.05). All patients who progressed and were rechallenged with LenDex responded. These analyses illustrate that discontinuation of lenalidomide after 1 year among those patients achieving a ≥VGPR can result in long‐term disease control. Am. J. Hematol. 89:302–305, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To study the impact of achieving stringent complete response (sCR), an increasingly attainable goal, after autologous stem-cell transplantation (ASCT) in patients with multiple myeloma (MM). Patients and Methods Maximal response rates were determined in 445 consecutive patients who underwent ASCT within 12 months of diagnosis of MM. The patients achieving varying degrees of complete response (CR) are the focus of our study. Results One hundred and nine patients (25%) achieved sCR after ASCT. The median overall survival (OS) rate from the time of transplantation for patients attaining sCR was not reached (NR), in contrast to those patients achieving conventional complete response (CR; n = 37; OS, 81 months) or near CR (nCR; n = 91; OS, 60 months; P < .001). Five-year OS rates were 80%, 53%, and 47% for sCR, CR, and nCR, respectively. The median time to progression (TTP) from ASCT of patients achieving sCR was significantly longer (50 months) than TTP of patients achieving CR or nCR (20 months and 19 months, respectively). On multivariable analysis, post-ASCT response of sCR was an independent prognostic factor for survival (hazard ratio, 0.44; 95% CI, 0.25 to 0.80; versus CR; P = .008), in addition to proliferation rate, pre-ASCT cytogenetics, and performance status. OS rates of patients attaining sCR continued to remain superior at 2-year landmark (median, NR v 70 months for conventional CR group; P = .007). Conclusion Improved long-term outcome is seen after ASCT with achievement of sCR when compared with lesser degrees of responses. Myeloma trials reporting the response rates should identify patients achieving sCR and CR separately, owing to markedly disparate outcomes of the two categories.

Purpose There is consensus that patients with light chain (AL) amyloidosis with hypercalcemia, renal failure, anemia, and lytic bone lesions attributable to clonal expansion of plasma cells (CRAB criteria) also have multiple myeloma (MM). The aim of this study was to examine the spectrum of immunoglobulin AL amyloidosis with and without MM, with a goal of defining the optimal bone marrow plasma cell (BMPC) number to qualify as AL amyloidosis with MM. Patients and Methods We identified 1,255 patients with AL amyloidosis seen within 90 days of diagnosis between January 1, 2000, and December 31, 2010. We defined a population of patients with coexisting MM on the basis of the existence of CRAB criteria (AL-CRAB). Receiver operating characteristic analysis determined the optimal BMPC cut point to predict for 1-year mortality in patients with AL amyloidosis without CRAB to produce two additional groups: AL only (≤ 10% BMPCs) and AL plasma cell MM (AL-PCMM; > 10% BMPCs). Results Among the 1,255 patients, 100 (8%) had AL-CRAB, 476 (38%) had AL-PCMM, and 679 (54%) had AL only. Their respective median overall survival rates were 10.6, 16.2, and 46 months (P < .001). Because the outcomes of AL-CRAB and AL-PCMM were similar, they were pooled for univariate and multivariate analyses. On multivariate analysis, pooled AL-CRAB and AL-PCMM retained negative prognostic value independent of age, Mayo Clinic AL amyloidosis stage, prior autologous stem-cell transplantation, and difference between the involved and uninvolved free light chain. Conclusion Patients with AL amyloidosis who have more than 10% BMPCs have a poor prognosis, similar to that of patients with AL-CRAB, and should therefore be considered together as AL amyloidosis with MM.

Abstract Smoldering multiple myeloma (SMM) bridges the gap between monoclonal gammopathy of undetermined significance (a mostly premalignant disorder) and active multiple myeloma (MM). Until recently, no interventional study in patients with SMM showed improved overall survival (OS) with therapy as compared with observation. A report from the PETHEMA-GEM (Programa Español de Tratamientos en Hematologica) group described both fewer myeloma-related events and better OS among patients with high-risk SMM who were treated with lenalidomide and dexamethasone. This unique study prompted us to review current knowledge about SMM and address the following questions: (1) Are there patients currently defined as SMM who should be treated routinely? (2) Should the definitions of SMM and MM be reconsidered? (3) Has the time come when not treating is more dangerous than treating? (4) Could unintended medical harm result from overzealous intervention? Our conclusion is that those patients with the highest-risk SMM (extreme bone marrow plasmacytosis, extremely abnormal serum immunoglobulin free light chain ratio, and multiple bone lesions detected only by modern imaging) should be reclassified as active MM so that they can receive MM-appropriate therapy and the paradigm of careful observation for patients with SMM can be preserved.

Key Points A continued monoclonal protein response after ASCT in the absence of further therapy is prognostic in MM patients.

Key PointsRadiation is appropriate primary therapy in approximately 25% of cases. Radiation provides long-term remissions in more than 50% of patients.