How I treat relapsed myeloma

Multiple myeloma (MM) is a plasma cell malignancy leading to significant life-expectancy shortening. Although the incorporation of the novel agents thalidomide, bortezomib, and lenalidomide in the front-line therapy has resulted in significant improvement, almost all patients relapse, making the treatment of relapse a real challenge. In the present article, when and how to treat relapsed MM is discussed. Treatment can be safely delayed in a subset of patients with asymptomatic relapse, whereas those with symptomatic relapse, advanced disease at diagnosis, or significant paraproteinemic increase require prompt rescue therapy. The benefit of retreatment and the use of a sequential approach for successive relapses considering drug synergism are highlighted. For patients with aggressive relapses and for those who have exhausted all available options, continued therapy until disease progression is recommended, particularly when using regimens with a long-term safety profile. Patients with a duration response to a first autologous stem cell transplantation (ASCT) longer than 2 years may benefit from a second ASCT. Patients with aggressive disease and/or poor cytogenetics at diagnosis relapsing within the first 2 years from ASCT should be considered for an allogeneic transplantation. Finally, a number of newer promising drugs are being actively investigated and the enrolment of patients in clinical trials is encouraged.

Pattern of Relapse and Progression After Autologous Stem-Cell Transplantation As Upfront Treatment for Multiple Myeloma

Abstract 3987 Background: Autologous stem cell transplantation (ASCT) is the gold standard as first-line treatment in young patients with multiple myeloma (MM). Prognostic factors have been usually related to patient characteristic and disease stage. Few investigations on the pattern of relapse or progression after ASCT have been addressed. The differentiation of serological or asymptomatic progression versus clinical relapse requiring treatment is also an important issue. The aim of this study was to investigate the characteristics at the time of relapse or progression in patients with MM who received ASCT as part of a first-line treatment. Patients and Methods: Two-hundred and eleven patients underwent melphalan-based ASCT at our institution during the last 18 years. Of these, 170 patients (87M/83F; median age 56 years, range 25 to 70) who achieved at the least a minimal response (PR) after no more of two induction lines before ASCT are the basis of this study. Initial baseline demographics, clinical and laboratory data at relapse or progression, and information concerning treatment and follow up were collected. The M-protein heavy-chain isotype was IgG (57%), IgA (23%), light chain only (14%) and others (3.5%). Only 2.5% were oligosecretory MM. Extramedullary plasmacytomas (EMP) were observed in 37 out of 170 patients (22%) at diagnosis. The ISS stage was I (45.3%), II (26.5%), III (18.8%) and unknown (9.5%). 12.6% of the patients had a serum creatinine level ≥2 mg/dL and 16.2% had hypercalcemia. The median follow-up for alive patients was 3.9 years (range 4 months to 18 years). Response, relapse, and progression were defined according to European Blood and Marrow Transplantation (EBMT) criteria. Results: Median PFS was 3.3 years (CI 95% 2.7 to 3.9 years) and the median OS of 6.8 years (CI 95% 3.9 to 9.6 years). 47.7% of the patients achieved a complete remission (CR). As of December 2011, 93 patients (54.7%) had relapsed or progressed after ASCT. 37 out of the 93 patients (40%) had relapsed from CR, while the remaining 60% had progressed from PR. A serological or asymptomatic relapse/progression was as frequent as a symptomatic one (49.5% vs. 50.5%, respectively), the latter requiring immediate treatment in the median of a month. Patients with serological relapse/progression had a significantly longer OS than those requiring immediate treatment (p=0.002)(Figure). The main clinical reasons to start myeloma therapy were anemia (43%), new bone lytic lesions (36%), EMP (23.7%), bone pain (14.4%), renal insufficiency (12.2%) and/or hypercalcemia (9%). 22 of the 93 patients (24%) relapsed/progressing patients had EMP at the time of progression. In three of them, the extramedullary involvement was the only criteria of progression. The presence of EMP at diagnosis was significantly associated with extramedullary disease at relapse (p=0.001). In fact, 12 out of the 22 patients (54.5%) with EMP at relapse had also EMP at the time of diagnosis. Median time between serological relapse or progression and treatment was of only 5.6 months (range 0 to 5.6 years). However, in 12 out of 46 patients (26%) with serological relapse/progression, treatment was not initiated within first two years. Finally, time to next treatment was significantly longer in patients relapsing from CR (median 2.85 years; CI 95% 2.1 to 3.6) vs. those progressing from PR (median 1.65 years; CI 95% 1.1 to 2.2) (p=0.017). Conclusion: After ASCT, serological or asymptomatic relapse/progression is observed in about one half of the patients. The treatment-free interval in these patients is longer in patients relapsing from CR than in those progressing from PR. Patients with symptomatic relapse/progression have shorter OS. Extramedullary involvement is frequent, being the highest risk in patients with EMP at diagnosis. Finally, relapse/progression with extramedullary disease only is rare. Disclosures: No relevant conflicts of interest to declare.

Role of FDG-PET/CT Surveillance for Patients with Classical Hodgkin's Disease in First Complete Response: The Stanford University Experience.

Abstract 1563 Poster Board I-586 Background In Hodgkin's Disease (HD) the role of FDG-PET/CT is well established in staging and assessment of treatment response, however, there is a paucity of data regarding its role in surveillance after first complete response (CR) has been achieved and treatment is completed. The purpose of this study was to evaluate reports of FDG-PET/CT scans performed in follow-up (fu) of patients (pts) in first CR and correlate results with freedom from progression (FFP) and overall survival (OS). We also sought to determine the proportion of surveillance scans that identified relapses in pts prior to development of clinical signs or symptoms. Patients and methods: We retrospectively identified pts with classical HD from the Stanford Hodgkin's Disease database who met the following predefined criteria; CR to primary treatment with all therapy and fu care at Stanford, FDG-PET/CT scans performed for the purpose of surveillance 0.3 to 5 years (y) after completion of therapy. Reports of surveillance scans were reviewed and scored as positive, if reported as suspicious for recurrence; indeterminate, if reported as likely consistent with a non-specific etiology; or negative, if there were no FDG-avid sites. Patient characteristics, therapy details, symptoms at fu visits and outcome were reviewed and clinical attributes correlated with FFP and OS. Results Between 3/2002 and 1/2009, 113 pts were identified who met the predefined criteria. Surveillance scans were performed as part of a study protocol in 33 pts and at physician discretion in remainder. The median age was 31y (range 18 to 71). 10 pts had stage I, 72 stage II, 12 stage III and 19 stage IV disease. Of the pts with stage I/II disease 52 were considered to have unfavorable risk factors based on either bulky mediastinal disease and/or additional criteria per European cooperative groups (ESR > 50, >2 AA sites, any extranodal [EN] sites). For the 31 pts with stage III/IV disease, International Prognostic Scores (IPS) were 1-2 (n=9), 3 (n=9) and ≥4 (n=13). Therapy consisted of Stanford V chemotherapy (SV) for 8 weeks (w) followed by involved field radiotherapy (RT) 20 Gy (n=31) or 30 Gy (n=10), SV for 12 w and 36 Gy RT to sites > 5cm and macroscopic splenic disease (n=57), BEACOPP (n=6), ABVD (n=7) and ‘other’ (n=2). Overall 326 scans were performed; y1 (n=123), y2 (n=103), y3 (n=68), y4 (n=26) and y5 (n=6). 30 pts had one or more reports consistent with a positive scan, 26 had indeterminate or negative, and 57 had only negative scans. At a median fu of 3.2y, the overall FFP was 87% and OS 100%. Only 14/30 pts (47%) with a positive scan relapsed; 9/82 (11%) of stage I/II pts and 5/31(16%) of stage III/IV pts. None of the pts with indeterminate or negative scans relapsed. The median time to relapse was 236 days (range 58 to 835). 12/14 (85.7%) relapses occurred within the first year and were not associated with clinical symptoms/signs in 9/12 (75%) pts. Two pts relapsed > 1y post CR (13 mo and 2.3 y) and symptoms prompted imaging with FDG-PET/CT in both. All pts were salvaged successfully with high dose chemotherapy and stem cell support. Conclusions Our retrospective data are consistent with other reports suggesting a high negative predictive value (100%) and low positive predictive value (47%) for FDG-PET/CT scans for surveillance in HD. In our data set most relapses identified by surveillance FDG-PET/CT imaging occurred within 1 yr of completion of therapy and were asymptomatic in 75% of pts. These relapses would have likely been missed in the absence of routine imaging. Whether early detection of asymptomatic relapse impacts outcome or not needs further testing. In our series, asymptomatic relapse beyond 1y was rare and our data do not support the practice of routine surveillance for all pts. Our data have important implications related to the interpretation of “positive scans” during surveillance, potential effects of radiation exposure from repeated FDG-PET/CT scanning as well as escalating health care costs. At this time the routine use of FDG-PET/CT surveillance requires further study and should be limited to prospective clinical trials. Disclosures No relevant conflicts of interest to declare.