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TO THE EDITOR: Allogeneic hematopoietic stem-cell transplantation (ASCT) is curative treatment for patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who otherwise have dismal outcomes.[1][1][⇓][2][⇓][3]-[4][4] The TP53 gene is located in the 17p13

Introduction Per the National Cancer Institute epidemiological data, the incidence of multiple myeloma has not changed significantly over the past decade. Mortality from myeloma has not changed significantly between 2007-2016 with an estimated 5-year survival of 55.2 % between 2009-2015. The treatment of multiple myeloma has improved significantly over the past decade with the approval of several new drugs. In the recent IFM trial, the 4-year overall survival in a select group of myeloma patients was 82% when treated with bortezomib, lenalidomide and dexamethasone followed by autologous stem cell transplant and maintenance therapy. These numbers may further improve with approval of monoclonal antibodies and several new drugs in clinical trials. The cost of healthcare has been growing consistently for the past several years. Per CMS data, healthcare spending grew 3.7% in 2017 reaching $3.5 trillion, or $10,739 per person. National health spending is projected to grow at a rate of 5.5% per year from 2018-2027 reaching nearly $6.0 trillion. Health share of the GDP is expected to rise from 17.9% to 19.4%. Pharmaceutical costs have been rising consistently over the past several years with cancer therapies being some of the costliest. Most new cancer therapy costs more than $100,000 per year with the triplet combinations for myeloma costing upwards of $200,000 per year. Methods Our goal was to evaluate the utilization of the newer drugs approved for myeloma by the Medicare population and assess the economic burden of growing drug prices on the health care system. We queried the national CMS database from 2013-2017 to obtain information on Medicare payments made, number of providers making claims and consulting fees for bortezomib, carfilzomib, daratumumab, elotuzumab, ixazomib, lenalidomide, panobinostat and pomalidomide. Results Between 2013-2017 there has been a significant increase in the annual Medicare payments made for myeloma drugs. The amount of payments has tripled between 2013-2017. The number of claims made and providers making those claims have increased. There has also been an exponential increase in consulting fees paid by various pharmaceutical companies to promote prescription of the aforementioned drugs. The amount of money paid in consultation has nearly quadrupled since 2013. Results are consolidated in Table 1 and Figure 1. Discussion This past decade has been an exciting period in cancer research and drug approvals, with myeloma being one of the many malignancies benefitting from this progress. This was made possible by the collaboration between pharmaceutical companies and academic institutions. With the need for continuous combination therapy in multiple myeloma along with increasing prices of existing drugs and high upfront market prices for newly approved drugs, there is significant financial burden placed on the healthcare system. Based on the published literature substitution of carfilzomib for bortezomib or addition of monoclonal antibodies in induction would double cost. Some of these drug approvals are based solely on surrogate endpoints of overall response rates and progression free survival benefit of few months. This is without proven overall survival data while harboring significant toxicity. Conclusion: With pharmaceutical companies spending millions of dollars for drug development there has been a trend towards higher drug pricing. These companies also pay large amounts of consulting fees to physicians dedicated to aggressively market these newly approved drugs which are priced higher than existing therapy. Some of the current cancer guidelines include authors who have financial conflicts of interest and receive consulting fees from pharmaceutical companies. It would be interesting to investigate the correlation between the consulting fees and its effect on prescription patterns. Even the cancer care guidelines do not consider the cost effectiveness of equally effective regimens. There has been a push from various pioneers in the field to incorporate value-based recommends into their guidelines. Given the trajectory of rising costs within our healthcare system, it is imperative for all physicians to be mindful of value-based care while seeking therapy options that provide true benefit to their vulnerable patient populations. Disclosures No relevant conflicts of interest to declare.

Introduction Outcomes after allogeneic stem cell transplant (AHSCT) are influenced by both disease and patient related factors. We hypothesized that combining hematopoietic stem cell transplant comorbidity-age index (HCT-CI/Age) and the refined disease risk index (DRI-R) would better predict survival post-transplant and developed a hematopoietic cell Transplant-composite risk (HCT-CR) model, which we tested in a group of patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) treated at MD Anderson Cancer Center (MDACC). Methods The study included consecutively treated patients, 18 years of age or older, with AML and MDS who received first AHSCT at MDACC between 2005-2016. Donors were HLA-matched related (MRD), HLA-matched unrelated (MUD), 9/10 MUD (MMUD), haploidentical (HAPLO) and 9/10 MRD (MMRD). To develop this model, patients were assigned into 4 groups: 1. Patients with low/intermediate DRI-R and HCT-CI/Age 3 (intermediate-risk); 3. Patients with high/very high DRI-R and HCT-CI/Age 3 (very high-risk). Primary endpoint was 5-year overall survival (OS); other outcomes assess were progression-free survival (PFS), non-relapse mortality (NRM) and relapse rate. The stability of the HCT-CR model was tested by bootstrap resampling. The discrimination power of the HCT-CR model on OS was compared with that of the DRI-R, HCT-CI/Age and cytogenetic risk model by the Harrell C-concordance index. Results The analysis included 942 patients (492 male and 450 female) with a median age of 53 years (range 18-65 years). Cytogenetic data at diagnosis was available in 928 (98.5%) patients and was favorable, intermediate and adverse cytogenetic risk in 63 (7%), 523 (56%) and 342 (37%), respectively. Fifty-five (6%), 399 (43%), 392 (42%) and 82 (9%) patients had low, intermediate, high and very high DRI-R, respectively. The HCT-CI/Age was available in 922 (98%) patients with the median score of 3 (range 0-18). Donor types included MRD (n=377), MUD (n=416), MMUD (n=68), HAPLO (n=73) and MMRD (N=8). Using the HCT-CR model, patients were stratified into 4 risk groups: low (N=272), intermediate (N=168), high (N=284) and very high-risk (N=184), with significantly different survival. The 5-year OS rates for patients in low, intermediate, high and very high-risk group were 57%, 48%, 34%, and 26%, respectively (P Compared with the low HCT-CR risk group, patients with intermediate, high and very high-risk group had a significantly increased risk of death with HR of 1.42 (95%CI 1.06-1.91; P=0.02), 2.11 (95%CI 1.65-2.70; P The stability of the hematopoietic cell transplant - composite risk model was confirmed in a bootstrap resampling procedure. Among 500 new datasets, on average, patients in intermediate, high and very high-risk group had significantly increased risk of death after transplant when compared with low risk group with HR of 1.39, 2.11 and 2.98, respectively. Results from the concordance test showed that the HCT-CR model provided better discriminative capacity for prediction of OS when compared with DRI-R, HCT-CI/Age and cytogenetic risk group models with C-index of 0.62 versus 0.60, 0.54 and 0.55, respectively. The goodness of fit test showed that the HCT-CR model fit the data significantly better than the other models (P Conclusion Combining disease and patient-related factors provides better survival stratification for patients with AML/MDS receiving AHSCT. This novel HCT-CR model will be validated in patients with all diseases undergoing allogeneic hematopoietic stem cell transplantation and results will be presented at the meeting. Disclosures Oran: ASTEX: Research Funding; Celgene: Consultancy, Research Funding; AROG pharmaceuticals: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Background: There have been significant improvements in the outcomes for patients with multiple myeloma over the past 10 years. The course of the disease remains highly variable. While some patients experience 10-15 year survivals, others succumb to highly refractory disease within a few months. Many studies have focused on the description of prognostic factors capable of predicting this heterogeneity in survival. Baseline Serum free light chain concentration is a major prognostic indicator for plasma cell neoplasms and normalization of free light chain ratio with treatment has been reported as an indicator for favorable prognosis. High Baseline free light chain concentration at presentation indicates aggressive disease. Furthermore High serum free light chain ratio correlates with elevated serum creatinine, elevated LDH and extensive marrow infiltration. Objectives: To determine if serum free light chain concentration > 1000mg/dl at the time of diagnosis and at disease progression was an independent prognostic marker for multiple myeloma. Methods: The results of all the serum free light chain analyses of patients evaluated at western Pennsylvania hospital between 2007 -2015 were reviewed and patients with serum free light chain concentration >1000mg/dl at the time of initial diagnosis and disease progression were identified Retrospective chart review was done to study the survival in these patients. Results: Total of 15 patients in whom serum free light chain concentration was greater than 1000 mg/dl at diagnosis were identified. Median age at diagnosis was 60.81 years (45.2-77.3). The median survival in this population is 1.85 years (range 0.06-8.85 years), with 5 deaths. Of these 15, 9 patients received an autologous PBSCT as a part of their initial therapy. Six of them are alive with a median overall survival of 2.44 years and mean survival of 3.89 years (range 0.87-8.89). In the remaining 6 patients that did not undergo an auto PBSCT 3 of them are alive with median overall survival of 1.21 years and a mean survival 1.20 years (range 06-2.76 years). There is an overall trend toward very poor prognosis in this specific group of patients irrespective of the age, sex, stage at time of diagnosis, the immunoglobulin subtype and the free light chain subtype (kappa vs lambda). We also conducted a retrospective review of patients in whom serum free light chains concentration was greater than 1000mg/dl at disease progression. Twenty patients were identified all of whom are deceased with a median overall survival from the time of progression with serum free light chains greater than 1000 mg /dl was dismal at 0.27 years and mean survival was 0.53 years (range 0.04-2.52 years) Conclusion: Patients with multiple myeloma who presented with a serum free light chain concentration greater than 1000 mg/dl at diagnosis have very poor prognosis. These specific subgroups of patients should be identified and treated aggressively at the time of diagnosis to prevent complications from multiple myeloma and improve their overall survival. In our small cohort of patients those who underwent auto PBSCT as a part of their initial therapy tend to have better outcomes in terms of overall survival compared to patients who received therapy without auto PBSCT consolidation. Patients with serum free light chains greater than 1000 mg/dl at disease progression will need to be treated aggressively with perhaps a salvage auto PBSCT to improve their overall outcome. A larger study to evaluate elevated serum free light chains (greater than 1000 mg/dl) as a prognostic indicator at diagnosis and progression should be done to further validate these findings Table 1 Table 1. Disclosures No relevant conflicts of interest to declare.

Objectives: To assess the efficacy and safety of da-EPOCH-R as frontline treatment for patients diagnosed with Stage III/IV Diffuse Large B-Cell Lymphoma. Methods: We conducted a retrospective study of newly diagnosed patients with advanced Diffuse Large B-Cell Lymphoma from January 2008 till September 2015, who received frontline da-EPOCH-R or R-CHOP at our Health System. We excluded patients with primary CNS lymphoma, primary testicular lymphoma and patients who received chemotherapy for a prior lymphoma. 25 patients who received da-EPOCH-R and 50 patients who received R-CHOP were identified. Da-EPOCH-R regimen consisted of Etoposide 50mg/m2/day, Doxorubucin 10mg/m2/day and Vincristine 0.4mg/m2/day given on Days 1-4, Cyclophosphamide 750mg/m2 on Day 5, Prednisone 60mg/m2 twice a day from Days 1-6 and Rituximab 375mg/m2given on Day 5. On Day 6 G-CSF was administered. Each cycle was given every 21 days for a total of 6 cycles. The dose of Etoposide, Doxorubucin and Cyclophosphamide was adjusted according to standard protocols. All patients on the da-EPOCH arm were on Acyclovir, Ciprofloxacin, Fluconazole and Trimethoprim-Sulfamethoxazole for anti-microbial prophylaxis during their treatment. The use of growth factors and anti-microbial prophylaxis was inconsistent in the R-CHOP arm. Results: When comparing the da-EPOCH-R arm versus the R-CHOP arm, the average age of the patients was 50 years (25-81) vs 60 years (19-84). High-risk IPI was similar in both arms (76% vs 74%). The percentage of non-germinal center type (non-GCB) was equal as well (36% vs 32%). The average number of cycles administered was 5.3 compared to 4.8. There were more dose reductions in the da-EPOCH-R arm (36% vs 24%), however fewer delays and cessations were noted (36% vs 54%). After a median follow up of 29.1 months, the age-adjusted overall survival (77% vs. 69%, p=0.093) and disease-free survival (76% vs. 55% p=0.54) was improved in the da-EPOCH-R arm. In the non-GCB variant da-EPOCH improved overall survival by 77% (p=0.024). The Overall Response Rate was higher in the da-EPOCH-R arm 80% (CR/CRU=64% and PR=16%) vs. 56% (CR/CRU=44% and PR=12%). The relapse rate was lower in the da-EPOCH-R arm (16% vs 28%), and it was lower in the non-GCB patients as well (11% vs 25%). There were more Grade 3-4 neutropenia in the da-EPOCH arm (72% vs 48%), however infectious complications were lower (24% vs 42%). There were fewer unplanned admissions in the da-EPOCH arm (32% vs 60%) and a significantly lower treatment related mortality (12% vs 22%). Other Grade 3-4 toxicities too were lower in the da-EPOCH-R arm (20% vs 30%). Conclusion: Our preliminary results suggest that da-EPOCH-R has a survival benefit especially in the non-GCB subgroup. Our data does show good survival data even for the GCB subtypes. There was a higher response rate, lower relapse rate and no added toxicities in patients who received da-EPOCH-R. A Phase III trial is currently ongoing and will provide us with answers regarding the efficacy and toxicities of this chemotherapy regimen. Disclosures No relevant conflicts of interest to declare.

Background: The addition of a Tyrosine Kinase Inhibitor (TKI) to induction chemotherapy has improved the outcome of patients with Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL). However, the treatment related mortality and morbidity of intensive treatment increases with age. The use of a TKI alone for induction is less toxic and yields CR rates comparable to combined therapy. Eligibility for post remission hematopoietic stem cell transplantation is less likely to be compromised with TKI induction. We present a retrospective review of patients with Ph+ ALL treated at our institution with dasatinib and prednisone induction who subsequently underwent allogeneic hematopoietic stem cell transplant (allo-HSCT) as post remission therapy. Methods: We retrospectively identified 15 patients with Ph+ ALL treated at our institution between February 2012 and June 2015. Patients received induction therapy with dasatinib at 100 mg or 140mg daily till complete hematological response. Prednisone 60 mg/m2/day (capped at 120 mg daily) was administered until day 24 and then tapered and stopped at day 32. Intrathecal chemotherapy with MTX and Ara-C were administered twice during the induction period. Dasatinib dose reduction/discontinuation was permitted for non-hematological toxicity. Patients who achieved remission proceeded to allo-HSCT if a suitable HLA-matched donor was available. Patients who did not have a suitable HLA matched donor received TKI + POMP maintenance. We calculated CHR, CCyR, disease-free survival (DFS) and overall survival (OS). Results: The median age of patients treated with dasatinib plus prednisone was 62 years (range: 19-73). Baseline patient and disease characteristics are summarized in Table 1. Median WBC count was 22.5 x 109/L. Fourteen of 15 patients treated with dasatinib achieved a CHR (93.3%), 1 patient did not undergo a bone marrow biopsy but had normal blood counts. Median time to CHR was 42 days (range: 22-69). CCYR was obtained in 11 patients (73%) and MMR was achieved in 5 patients (33%). No patient died during induction therapy. The 14 patients who were in CHR after induction, underwent allo-HSCT (n=7), are being evaluated for allo-HSCT (n=3), were unable to undergo allo-HSCT due to a high comorbidity index and/or lack of a suitable donor (n=3) or were lost to follow-up (n=1). Of the 3 patients who were unable to undergo allo-HSCT, 2 patients continue on dasatinib maintenance and 1 patient takes ponatinib. Of 8 patients not yet transplanted 3 relapsed, while only 1 relapse was seen in 7 patients who underwent allo-HSCT. Median DFS was 315 days (range: 57-1061) and median OS was 354 days (range: 107-1082) corresponding Kaplan Meier curves for OS and DFS are shown below. Conclusions: In our adult Ph+ ALL patients induction therapy with dasatinib and prednisone was effective and well tolerated. Patients achieving CHR were able to undergo allo-HSCT with curative intent. This strategy retrospectively appears equal or better than results with induction chemotherapy of conventional variety. Table 1. Patient characteristics Male sex, n (%) 5 (33.3) Age Figure 1. Overall Survival. Figure 1. Overall Survival. Figure 2. Disease Free Survival Figure 2. Disease Free Survival Disclosures Fazal: Novartis: Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Ariad: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau. Off Label Use: Dasatinib use for newly diagnosed Ph+ ALL.