Gertz, Morie A.

8603 Background: Steroids, primarily dexamethasone (Dex), remains an integral part of the therapy for myeloma. Prior to the advent of novel agents, Dex as a single agent was demonstrated to produce overall response rates of around 50%. The toxicity associated with pulsed high dose Dex has led to this approach being abandoned. This study investigates whether responsiveness to Dex correlates with biological qualities of the plasma cell clone that predicts outcome. Methods: We identified from our prospectively maintained database, patients with newly diagnosed myeloma, who were seen at Mayo Clinic within 30 days of diagnosis and were treated with single agent Dex. The M-protein measurements and responses were assessed using the IMWG criteria. Results: 182 patients seen between March 1998 and June 2007, initially treated with single agent Dex for at least 4 weeks, were included in the analysis. The median age at diagnosis was 63 (range; 39–81) and 59% were male. The actuarial median survival for the entire group was 55 months. The median duration of Dex therapy was 15 weeks (range; 4–193). Ninety one (50%) had a partial response or better and 11 (6%) were not evaluable, with the remaining patients (44%) having less than PR or progression. 10 patients (5%) achieved a VGPR or CR. The median overall survival from diagnosis for the 91 responders was 75 months compared to 71 months for the remaining patients; p = 0.6. There was no correlation between baseline disease characteristics and Dex responsiveness. One hundred thirty (70%) patients proceeded to an autologous SCT after a median of 15 weeks (range 1–46 months) of Dex. While the median overall survival was longer among the group of patients who underwent SCT, among either group, there were no survival benefit between those with a PR or better to Dex compared to the rest. Conclusions: Among this group of patients with newly diagnosed myeloma treated with single agent Dex, failure to respond to Dex induction therapy did not impact overall survival. Failure to respond to single agent steroid does not have an adverse impact on outcome in newly diagnosed myeloma. [Table: see text]

8513 Background: Waldenström's macroglobulinemia is a low-grade lymphoplasmacytic lymphoma that is responsive to rituximab. Uniform response criteria define an objective response as a 50% reduction in the IgM level, and a minor response as a 25% reduction in IgM level. No publications in the literature exist that justify the use of the minor response. Clinicians who treat patients that achieve a minor response are left uncertain as to whether the response is adequate and patients should be monitored for progression or whether they should be considered therapy failures and crossover to an alternate chemotherapy regimen in an effort to achieve a deeper response. Methods: 69 patients, 34 previously untreated, and 35 previously treated (but rituximab naive) were included. All patients were treated with a single four-week course of rituximab 375 mg/m2 and were monitored with no further therapy until progression. Results: There were 19 objective and 17 minor responses out of 69 eligible patients (52.2%). Response rate and progression-free survival (26.6 mo) were similar whether patients were previously untreated or previously treated. Previously treated rituximab-naïve and previously untreated patients had, five-year survivals of 48% and 85%, respectively. There was no difference in overall or progression free survival between patients who achieved an objective response when compared to those who achieved a minor response. There was no difference between objective and minor responders by age, time from diagnosis to treatment in the treated group, bone marrow lymphoplasmacytes, hemoglobin level, creatinine, IgM level, or M-spike. The pre-treatment level of IgM did not predict overall survival, progression-free survival, time to progression, or response rate (All p>0.05). This lack of significance was found whether IgM was assessed as a continuous or discrete variable. Conclusions: These results reconfirm rituximab's efficacy as a single-agent for the treatment of Waldenström's macroglobulinemia, and patients who have a 25–50% reduction in their IgM protein derive significant clinical benefits that are durable and appear to not have an impact on overall survival. No significant financial relationships to disclose.

e19513 Background: The outcome of patients with MM relapsing after ASCT used early in the disease course or after failure of initial therapy, is not well defined. We undertook this study to understand treatment approaches for patients relapsing after single ASCT. Methods: Patients relapsing after single ASCT were identified from a prospectively maintained database and relevant clinical data were extracted from medical records. Relapse and treatment responses were according to IMWG Uniform Response Criteria. Patients relapsing between Jan 2000 and 2008 were included in order to capture a recent cohort contemporaneous to availability of novel drugs. Results: We studied 487 patients who had relapsed following a single ASCT, of whom 351 (72%) had an early SCT (≤ 12 mos from diagnosis). The median estimated follow up for all patients was 27 mos, 50 mos and 69 mos from relapse, SCT and diagnosis respectively. The median overall survival (OS) from the time of relapse was 30 mos for the early SCT group and 21 months for the late SCT group. The median time to relapse following transplant was 15 mos (3–119) among early SCT group and 12 mos (3–76) among the late SCT group. Longer time to relapse as well as longer time from relapse to initiation of therapy were independent predictors of better outcome. Among the early group, nearly a third of the patients achieved a PR or better to first salvage therapy (Table), with another third achieving stable disease and 25% of patients did not have response data. The median progression free survival for the first salvage regimen was 8 mos; 18 mos for those with PR or better and 5 mos for those with SD as the best response. Data on the regimen 2, 3, 4, 5, and 6 were available for 211, 133, 84, 53 and 28 patients respectively. As expected, the response rates and the response duration decreased with increasing number of relapses. Conclusions: Patients relapsing after ASCT can obtain prolonged response duration with the currently available treatments. Those with a durable response to transplant and those not requiring initiation of therapy for long periods after disease relapse have favorable disease biology and have prolonged survival after relapse. The natural history of the disease provides a valuable benchmark for evaluation of newer treatment approaches. No significant financial relationships to disclose.

7039 Background: Erythropoiesis-stimulating agents are known to increase the risk for VTE events, especially in patients with underlying malignancies. However, there is a paucity of information on other hematopoietic growth factors such as granulocyte colony-stimulating factor (GSCF) granulocyte-macrophage colony stimulating factor (GM-CSF) AMD 3001 and risk for VTE. Methods: Between January 2000 and October 2008, a total of 631 patients underwent peripheral blood stem cell mobilization (PBSCM) using either GCSF, GMCSF, cyclophosphamide, AMD 3100, or with any of the above combination. We included only patients with a diagnosis of AL amyloidosis (AL), multiple myeloma (MM) Hodgkin's lymphoma (HL) and non Hodgkin's lymphoma (NHL). Patients’ demographic details and diagnosis of VTE were collected from electronic medical records. Results: Of the 631 patients who underwent PBSCM the median age of the patients was 57 years (range 17–77). 448 patients (71%) received single agent GCSF, 82 (13%) received combination of GMCSF and cyclophosphamide, 52 (8%) received cyclophosphamide and GCSF, 30 patients received a combination of GMCSF and GCSF, 10 (1.5%) patients received GCSF and AMD 3100. Of the 631 patients, 278 (44%) MM, 209 (33%) NHL, 114 (18%) AL, and 20 (3%) had HL. We found 7 (1.1%) patients with symptomatic VTE occurring between administration of growth factors and stem cell transplant. The median duration from the administration of growth factors to detection of VTE was 5 days (range 1–30). Two AL,3 MM and 2 NHL. Of the 7 patients, 2 patients had pulmonary embolism and 1 patient developed deep vein thrombosis. Two patients with AL developed heparin induced thrombocytopenia (HIT). The remaining 4 patients developed symptomatic catheter related thrombosis. Only 1 patient had past history of VTE. Of the 7 patients, 5 received GCSF alone, 1 received GMCSF, and cyclophosphamide, 1 received GCSF and cyclophosphamide. Of the 4 patients who developed catheter related thrombosis, catheter was removed in 2 patients. None of the patients developed VTE related morality. Conclusions: The risk for symptomatic VTE during PBSCM is low. HIT should be considered as a possible cause for VTE in patients undergoing PBSCM. No significant financial relationships to disclose.

Abstract A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)–, immunomodulatory drug (iMiD)–, or PI plus IMiD–based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P < .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P < .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P < .001). Gain of >1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.

AbstractResponse assessment in light chain (AL) amyloidosis is based on serum and urine monoclonal protein studies. Newly diagnosed patients (n = 373) who achieved very good partial response or complete response (CR) to first line therapy were assessed for the survival impact of each of the monoclonal protein studies. At end of therapy (EOT), negative serum/urine immunofixation (IFE) was achieved in 61% of patients, 72% achieved normal serum free light chain ratio (sFLCR), and the median involved free light chain (iFLC) and difference between involved to uninvolved light chain (dFLC) were 17 mg/L and 5 mg/L, respectively. Overall, 46% of patients achieved a CR at EOT. At EOT, iFLC ≤20 mg/L and dFLC ≤10 mg/L were additive in survival discrimination to negative serum/urine IFE and were independent predictors of overall survival. In contrast, normalization of sFLCR did not add survival discrimination to serum/urine IFE and was not independent predictor of survival. We propose a new definition for hematological CR to include serum/urine IFE negativity plus iFLC ≤20 mg/L or dFLC ≤10 mg/L, instead of the current definition of serum/urine IFE negativity and normal sFLCR. Complete response using dFLC ≤10 mg/L had the best performance in those with significant renal dysfunction and by light chain isotype, making it the preferred partner to IFE. Validation of these results in a multicenter cohort is warranted.

AbstractTransplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.