ALBERT

Description: Abstract 4464 BACKGROUND: Standard therapy for multiple myeloma (MM) includes initial autologous hematopoietic cell transplantation (autoHCT1) but this is not curative and most patients will relapse. Data on salvage autoHCT2 or allogeneic HCT (alloHCT2) are limited and the optimal salvage strategy is unknown. METHODS: Retrospective review of MM patients over 18 years of age who relapsed after autoHCT1 and underwent salvage autoHCT2 or alloHCT2 between 1995–2011 at our institution. Tandem auto-autoHCT or auto-alloHCT were excluded. Disease response was defined by the International Myeloma Working Group criteria and assessed 100 days after HCT2. RESULTS: Patient characteristics of autoHCT2 (N=27) and alloHCT2 (N=19) (Table 1) were not significantly different except the alloHCT2 median age was significantly lower (54 years) than for autoHCT2 (62 years) and more alloHCT2 patients had KPS 70% or more. Median followup of both groups was 57 months. Complete and very good partial remission (CR/VGPR) improved from 7% to 56% after autoHCT2 and from 26% to 37% after alloHCT2. Of 15 patients with progressive disease (PD) who had autoHCT2, 5 achieved CR/VGPR with 7 PR. Nonrelapse mortality (NRM) at 1 year was 3.7% for autoHCT2 and 5.3% for alloHCT2 (p=.901). Median progression free survival (PFS) and overall survival (OS) for autoHCT2 (19 months, 23 months) and alloHCT2 (6 months, 19 months) were not significantly different (p=0.156 and p=0.255). On multivariate analysis, time from autoHCT1 to relapse less than 1year vs. 1year or more (HR 24.81 [95% CI 2.4–249.9]) and no maintenance therapy vs. given after autoHCT2 (HR 12.19 [95% CI 2.5–249.9] impacted OS after autoHCT2. On multivariate analysis, only time from autoHCT1 to relapse less than 1 year vs. 1 year or more (HR 18.55 [95% CI 2.28–150.57]) impacted PFS after autoHCT2. For alloHCT2, no factors impacted NRM, PFS or OS including chemosensitivity, acute/chronic GVHD, donor lymphocyte infusion, antithymocyte globulin, reduced intensity vs. myeloablative conditioning, matched sibling or unrelated donor, time from autoHCT1 to relapse less than 1 year vs. 1 year or more. For those with relapse from autoHCT1 less than 1 year vs. 1 year or more undergoing autoHCT2, median OS was 15 months (0–53) vs. not yet reached (p=0.003) and median PFS was 5 months (0–49) vs. not yet reached. (p=0.002) Major causes of death for alloHCT2 were PD (n= 5), GVHD (n=3), while for autoHCT2, PD (n=10), infection (n=3). CONCLUSIONS: Salvage autoHCT2 and alloHCT2 are both feasible for patients with post autoHCT1 MM relapse. Relpase 1 year or more from autoHCT1 predicts for better PFS and OS in the autoHCT2 group. Those with progressive disease can also be salvaged by autoHCT2. Maintenance therapy after autoHCT2 is beneficial and should routinely be used. Disclosures: No relevant conflicts of interest to declare.

Description: With the new treatments for multiple myeloma (MM), increasing numbers of patients fail to mobilize sufficient peripheral blood stem cells (PBSC) for autologous stem cell transplant (ASCT). Multiple studies have identified clinical and laboratory factors, such as age, number of lines of chemotherapy, radiation exposure, bone marrow involvement, and low PLT count as risks for poor mobilization. However, there are fewer studies that analyze only the effect of multiple clinical risk factors on mobilization outcomes. We retrospectively analyzed 259 MM patients who underwent first apheresis after GCSF mobilization between December 2000 and December 2012. Clinical risk factors analyzed include age, number of lines of chemotherapy, number of cycles of chemotherapy, number of doses of cyclophosphamide, number of doses of lenalidomide, and prior external beam radiation. The standard dose of GCSF was 10 mcg/kg/day, however the exact dose for a significant number of patients was not known. Patients were assessed as to whether optimal (≥8x106 CD34+ cells/kg) or minimal (≥4x106 CD34+ cells/kg) number of stem cells for two ASCTs were collected. The median age of the entire cohort was 59.7 years (27.9-76.0). Overall 10.8% and 32.6% failed to collect the minimal and optimal number of stem cells after one round of apheresis. Of the twenty patients who underwent a second round of apheresis, 9 (45%) collected minimal and 7 (35%) collected optimal total number of stem cells, with an overall failure rate of 4.6% and 29.8%, respectively. The effect of the number of clinical risk factors on the mobilization failure during first apheresis is summarized in Table 1. For each additional clinical risk factor, the likelihood of collecting the minimal and optimal number of CD34+ cells is reduced by 34% (CI=0.484-0.893, p=0.0072) and 32% (CI=0.538–0.860, p=0.0013) respectively. On univariate analysis, all risk factors were analyzed as continuous variables, except for prior radiation which was analyzed as a categorical variable. Prior lenalidomide exposure (odds ratio=0.502, CI=0.297–0.845, p=0.0096), and prior radiation therapy (odds ratio=0.502, CI=0.293–0.861, p=0.0123) had the greatest negative predictive value. Of the 38 patients who were exposed to lenalomide (median 4 cycles; range 1-24 cycles), 13% and 42% failed to collect minimal and optimal number of stem cells in the first apheresis cycle, respectively. An association was seen between number of days required to collect target number of stem cells and number of risk factors (p≤0.001). Median number of days required to collect target number of stem cells for 0, 1 or 2+ clinical risk factors was 2, 2, and 4 days, respectively. When the effect of clinical risk factors were analyzed according to number of CD34+ cells/kg collected on each day of apheresis, statistically significant differences in collection efficiency were seen on the first 3 days of apheresis (Figure 1). In summary, clinical characteristics of patients with MM can potentially be used to predict mobilization failure. The presence of 2 or greater clinical risk factors adversely affect the ability to successfully collect the target stem cell dose. These risk factors may help in identifying high-risk MM patients who may benefit from alternative mobilization regimens that can be tested in prospective clinical trials.Number of Clinical Risk Factors012+N1128561% Patients not collecting optimal # of cells on 1st apheresis cycle23.231.850.895% CI15.8-32.122.1-42.833.7-63.9p-value0.19710.0003% Patients not collecting minimal # of cells on 1st apheresis cycle5.411.818.095% CI2.0-11.35.8-20.69.4-30.0p-value0.11950.0096Median number of days of collection224Range1-81-91-10p-value0.4233

Description: Background: Daratumumab (Dara) was recently FDA approved for the treatment of relapsed/refractory multiple myeloma (RRMM). We evaluated a real-world single-center experience of Dara salvage therapy for RRMM. Methods: Patients treated at the University of Florida with Dara for RRMM between January 2016 and February 2018 were included. Data was collected by chart review and analyzed for patient demographics, disease characteristics, treatment, and outcomes. Results: 25 patients (13 as monotherapy and 12 in combination) were included, with a median age of 63 (range, 42-86) years. Median time from MM diagnosis to Dara initiation was 51.3 (range, 8.4 -162.3) months. The median duration of Dara therapy was 72 days (range, 7 - 622). The median number of Dara doses was 7 (range, 2- 49). The best response to DARA was Very Good Partial Response (VGPR) in 1 (4%), Partial Response (PR) in 17 (68%), while 7 (28%) had Progressive Disease (PD). Overall Response Rate (ORR) to Dara was 72%. By the end of the study period, another 11 (44%) patients progressed while on DARA with a total of 18 (72%) patients having PD at the time of analysis. Estimated median progression free survival (PFS) after starting Dara was 155 days (95% CI: 21 - 289) and estimated median overall survival (OS) in the entire cohort was 11.7 months (95% CI: 4.2 - 19.2). Post DARA, 1 (4%) patient with VGPR underwent ASCT, while 9 (36%) went on to have other therapies which included HyperCVAD, Melphalan, and clinical trials, and 8 (32%) were treated with only best supportive care. Of 18 patients who had PD, 10 (40%) patients had a progressive extramedullary disease (EMD), of whom 6 (24%) had EMD prior to starting Dara, while another 4 (16%) patients developed new EMD while on Dara. PFS in the EMD cohort was 63 days (95% CI: 23 - 103), which was shorter than patients with no EMD (333 days; 95% CI: 42 - 624) (P= 0.08). Estimated median OS in patients with EMD was 5.4 months while in patients with no EMD was 16.1 months (p =0.16). Conclusions: DARA therapy does have good ORR (72%) in RRMM, however, there was an unusually high incidence of progressive or newly diagnosed EMD in RRMM patients treated with Dara/Dara-containing regimens, suggesting that Dara may not be effective in treating or preventing EMD. Moreover, we noticed patients who have EMD or develop new EMD tends to have worse outcomes. The underlying escape mechanism for EMD remains unknown and warrants further investigation. Table. Table. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 4748 Hematopoietic Stem Cell Transplant Comorbidity Index (HCT-CI) Scores Correlates with Increased Readmissions and Days in Hospital in Patients Undergoing Myeloablative Hematopoietic Stem Cell Transplantation. Ellen Szwed, Jack W. Hsu, Wei Hou, Randy A. Brown, Christopher R. Cogle, John W. Hiemenz, W Stratford May, Jan S. Moreb, Baldeep Wirk, John R. Wingard. The hematopoietic stem cell transplant comorbidity index (HCT-CI) was developed to assess the impact of comorbidities in allogeneic stem cell transplant (AlloSCT) recipients. It has been shown to correlate with non-relapse mortality and overall survival in both the myeloablative, non-myeloablative (NMA), and reduced intensity (RIC) settings, regardless of graft source. However, the economic impact of allogeneic transplant in patients with comorbidities has not been assessed. We retrospectively analyzed 181 consecutive patients who underwent AlloSCT from an HLA identical sibling following either myleoablative (n= 109) or NMA/RIC (n=71) conditioning regimens between January 2001 and December 2008. The HCT-CI score was calculated according to the method of Sorror, et al. (Sorror ML, et al. Blood. 2005 106: 2912–2919). Median follow-up of the entire cohort was 2 years. As previously published, there was a statistically significant correlation between HCT-CI and both non-relapse mortality (HR = 1.147, p = 0.0170,) and overall survival (HR = 1.152, p=0.0001) at 2-years of 23% and 50% respectively. We found statistically significant correlations between the HCT-CI score and total number of hospital readmissions (mean = 1.92; r=0.192; p = 0.0098) and total days in hospital after initial discharge from hospital after stem cell infusion (mean = 22.4 days; r=0.156; p = 0.036). Interestingly, the correlation for number of hospital days did not become statistically significant until 180 days or greater after transplantation. There was no correlation between HCT-CI with graft source, relapse or graft-vs.-host disease. When we stratified the HCT-CI to either myeloablative (N=109) or NMA/RIC (N=71) conditioning regimens, the correlations between the HCT-CI and both non-relapse mortality and overall survival were still statistically significant. The differences in days of hospitalization remained statistically significant in the myeloablative setting, but not in the NMA/RIC setting. In conclusion, our analysis of AlloSCT recipients found a correlation between the HCT-CI and the number of readmissions and hospital length of stay for myeloablative but not NMA/RIC conditioning regimens, suggesting a higher HCT-CI score results in greater use of hospital resources and costs. The increase in resource utilization is greater after the immediate post-transplant period. Whether these conclusions also apply in other transplant settings will need to be investigated. Disclosures: No relevant conflicts of interest to declare.

Description: Background Early response to induction therapy for AML assessed by bone marrow (BM) evaluation on day 14 (D14) post chemotherapy is considered an important predictor of achieving complete remission (CR). Our aim was to identify clinical and laboratory factors influencing the probability of CR in AML patients (pts) with positive D14 BM without receiving further chemotherapy. Methods Records of pts with AML treated between 1998 and 2011 were retrospectively reviewed to identify subjects with positive D14 BM who did not receive re-induction chemotherapy. The distribution of following variables such as age, white blood cell count (WBC) at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk was compared by the univariate analysis. Recovery BM status (positive vs. negative for disease) as the response variable and age, WBC at the time of induction therapy, BM cellularity, percentage of blasts, disease status, and risk as explanatory variables were assessed by the logistic regression analysis. Poor risk AML was defined as the presence of adverse karyotype, treatment related disease or presence of antecedent hematologic disorder. Positive BM was defined as either cellularity ≥20% or ≥5% myeloblasts by IHC staining. CR was defined according to IWG 2003 criteria. Results 169/378 (44%) had a positive D14 BM after induction therapy and 92/169 (54%) did not receive re-induction chemotherapy. 68/92 (74%) underwent repeated BM evaluation at WBC recovery, which occurred 4-5 weeks after induction chemotherapy. Recovery BM showed refractory AML in 38/68 (56%) of cases. However, in 30/68 (44%) cases CR was achieved despite previously positive D14 BM. As demonstrated in Table 1, clinical and laboratory characteristics of the CR and refractory groups showed significant differences in the absolute percentage of D14 myeloblasts, abnormal vs. normal myeloblast phenotype, de novo vs. relapse disease status, and risk stratification. Higher blast percentage (P=.0016) was associated with significantly higher probability of having refractory AML and each 1% increase blasts on D14 BM increased the odds of refractory AML on recovery BM by 6% (OR=1.06 95% CI 1.022-1.099) (Figure 1) In contrast, no clear association between D14 BM cellularity and the recovery BM status was found. The results from the multivariate analysis were comparable with that from the univariate analysis. Blast percentage, disease status, and AML risk were strongly and jointly associated with the status of BM recovery. By using a logistic model including myeloblast percentage, myeloblast phenotype, disease status, and AML risk category we correctly predicted 31 refractory AML cases out of 38 (sensitivity = 82%) and we correctly predicted 23 CR cases out of 30 (specificity = 77%). For example, based on our formula, which incorporated blast percentage, disease status, and AML risk we estimated that in a patient with de novo, not a poor risk AML with 5% blasts on D14 BM the probability of positive recovery BM status was 6%, whereas in a patient with relapsed poor risk AML and 50% blasts on D14 BM the probability of positive recovery BM status was 98%. Conclusions Significant proportion of pts with positive D14 BM may achieve CR without subsequent chemotherapy administration. Low blast percentage, absence of phenotypically abnormal myeloblasts, de novo diagnosed AML, and absence of poor risk AML are associated with a significantly higher probability of CR. We developed a useful formula for predicting remission status in the setting of positive D14 BM that would be valuable in clinical trial protocols involving decision trees for re-induction chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Introduction: Although melphalan at a dose of 140 mg/m2 (MEL-140) is known to be an effective preparative regimen for autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma (MM) patients, there are very few studies comparing it to the most commonly used dose of 200 mg/m2 ( MEL-200). Methods: We retrospectively reviewed the records of all myeloma patients who underwent an ASCT between 2001 and 2010 at our institution. We then identified patients who received melphalan as their preparative regimen at doses of 140 mg/m2 or 200 mg/m2. Patients who received any other drug as conditioning regimen or had more than one ASCT or had documented amyloidosis were excluded. Data were collected for variables known to possibly affect prognosis of MM patients. We assessed effect of melphalan dose on toxicities and outcomes. Results: A total of 129 eligible patients were identified, with 33 receiving MEL-140 and 96 receiving MEL-200. As was expected significantly higher percentage of patients in the MEL-140 arm were older than 65 years (P= 2 either at diagnosis (P=0.004) or the time of ASCT (P=0.001). Rest of the patient and disease characteristics including Durie-Salmon stage, myeloma subtype and disease status at ASCT were not significantly different between the 2 arms. Patients in MEL-140 needed significantly longer time to ANC engraftment (P=0.037) and also had significantly higher frequency of neutropenic fever (P=0.003). There were no significant differences in mucositis (including grade), nausea, vomiting, diarrhea, bacteremia, or length of hospital stay and frequency of repeat hospitalizations among both groups. There was no treatment related mortality in either group. At a median follow up of 74 months (range, 52-140) from ASCT, there were no significant differences in relapse free survival (RFS) (P=0.4988) and overall survival (OS) (P=0.6936) between the two groups. Five year OS for MEL-140 and MEL-200 is 71.6% and 78.9%, while RFS is 23.9% and 34%, respectively. Proportion of patients whose myeloma status improved to ≥ VGPR at 3 months post ASCT was also not different (P=0.385). Importantly, similar proportions of patients received various post ASCT maintenance therapy (P=0.605). In multivariate cox proportional hazards model only disease status of ≥VGPR at the time of ASCT significantly affected RFS (P=0.024) but did not impact OS (P=0.104). Conclusion: MM patients who received MEL-140 had similar long term outcomes as those who received MEL-200 despite their older age, lower performance status and renal insufficiency. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Persistent AML is a known risk factor for poor outcomes after allo-HCT. The impact of MRD in patients who achieve complete remission (CR) or CR with incomplete count recovery (CRi) has been less well studied. Methods: We retrospectively reviewed the records of AML patients who underwent allo-HCT in morphological remission ( CR1 10 (26%) 31 (24%) Allo-HCT after1st relapse(〉CR1): duration of CR1 〉 12 mo 31 (82%) 113 (88%) 0.285 ≤ 12 mo 7 (18%) 15 (12%) Secondary AML No 23 (60%) 78 (61%) 0.964 Yes 15 (40%) 50 (39%) Complete remission vs CRi CR 28 (74%) 110 (86%) 0.077 CRi 10 (26%) 18 (14%) Conditioning Regimen Ablative 24 (63%) 72 (56%) 0.449 Other 14 (37%) 56 (44%) Donor Type Matched sibling donor 12 (32%) 42 (33%) 0.887 Other 26 (68%) 86 (67%) Female donor: male recipient (FDMR) Other 28 (80%) 91 (78%) 0.844 FDMR 7 (20%) 25 (22%) Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Although day D14 BM after initiation of induction chemotherapy is accepted standard of care in AML patients (pts), it has poor predictive value and low accuracy for refractory disease. Currently there are no established clinical and laboratory factors which accurately predict which AML pts with positive D14 BM require immediate reduction chemotherapy for persistent disease and which pts achieve complete remission (CR) Methods: We retrospectively analyzed pretreatment factors and post-induction response in AML pts to determine if clinical and laboratory characteristics can improve the predictive value of the D14 BM evaluation. Results: Among 297 pts with D14 BM biopsies, 183 pts (61%) had positive D14 BM (either ≥ 5% myeloblasts or cellularity ≥ 20%). Of those with a positive D14 BM biopsy, no reinduction chemotherapy was given to 89 pts of which 57 (64%) pts had persistent disease at count recovery and 32 (36%) pts achieved CR. Persistent disease at count recovery after positive D14 BM was more likely associated with higher percentage of D14 myeloblasts, history of relapsed disease, and poor-risk disease category than pts with positive D14 BM who achieved CR. Age, D14 BM cellularity, and WBC at first day of induction chemotherapy had no significant influence on remission status in pts with a positive D14 BM (Table 1). We developed, and tested in a validation cohort, new prediction model using both D14 BM status and clinical/laboratory factors such as the percentage of blasts, history of relapsed disease, and poorer disease risk category. Then we compared results of this prediction model to that of D14 BM alone without the usage of clinical/laboratory prognostic factors. Our prediction model significantly improved the positive predictive value (84% vs.64% P=0.001) and the accuracy of prediction of recovery marrow status (0.88% vs. 80%, P=0.002) in AML pts with positive D14 BM (Table 2). Conclusion: In this study we developed and validated a new prediction model for interpreting D14 BM biopsies in AML pts after induction chemotherapy. With the addition of readily available clinical and laboratory information, our multivariable model provides a more accurate prediction of recovery bone marrow status and identification of patients with positive D14 BM who may not benefit from early reduction chemotherapy. Table 1. Clinical and Laboratory Characteristics of AML Patients with Positive D14 BM Who Did Not Receive Immediate Reinduction Chemotherapy. Persistent AML at count recovery CR+CRi P value Number 57 32 Age, years Median (min, max) 59 (19, 75) 55.5 (20, 78) 0.064* WBC Count at Induction, x 109/L Median (min, max) 5.7 (0, 285) 3 (0, 95) 0.25* D14 Cellularity, % Median (min, max) 10 (5, 40) 10 (3, 60) 0.079* D14 Blasts, % 0-10 10%-30 〉30 13 20 24 15 13 4 0.0023* Disease Status Before Induction Therapy De novo Relapsed 19 38 26 6

Description: Background In spite of recent improvements in survival, multiple myeloma (MM) remains an incurable disease.  Following autologous stem cell transplantation (ASCT), maintenance therapy has been shown to improve progression free survival (PFS) but data on overall survival (OS) is mixed.  The expense of therapy is significant and a substantial number of patients are unable to tolerate its toxicity.  In this study, we report our experience with the use of oral cyclophosphamide ± prednisone (CY) as an alternative for these patients.  Methods From January of 2000 to December of 2010, we retrospectively evaluated all patients with MM who underwent ASCT at our institution and separated them into four groups depending on maintenance therapy: No maintenance, interferon ± prednisone (IFN/Pd), IMIDs, and CY.  Patients who received maintenance after their first relapse were analyzed separately for tolerability, PFS, and OS.  Survival data was analyzed by logrank test and the group characteristics were compared using an unpaired t-test.    Results A total of 288 patients underwent ASCT at our institution from 2000 to 2010.  Of these patients, 8 were excluded due to insufficient follow-up.  1 patient who received bortezomib was also excluded. The median age at diagnosis was 58.0 years and the median time from diagnosis to ASCT was 8.3 months.  Collectively, this cohort included 193 Caucasians, 64 African Americans, 16 Hispanics, 4 Asian and 2 unknown race; 55.7% were men and 44.3% were women.  Following ASCT, 112 patients received no maintenance therapy, 74 of them (66.1%) had documented relapses with a median PFS of 18.2 months.  78 patients received IFN/Pd; 55 of them (70.5%) relapsed with a median PFS of 18.4 months. Alternatively, 79 patients were treated with IMIDs with 40 known relapses (50.6%) and a median PFS of 22.5 months.   CY maintenance was used in 10 patients; six patients relapsed within a median time of 20.4 months.  Collectively, maintenance therapy was associated with a significant improvement in PFS (22.5 vs. 18.2 months, p=0.037) but no difference in OS (45.5 vs. 43.9 months, p=0.29).  Among patients treated with maintenance therapy, PFS was superior in the group treated with IMIDs compared to IFN/Pd (22.5 vs. 18.4 months, p