Upfront Autologous Hematopoietic Stem Cell Research Articles

Long-term remission after upfront autologous hematopoietic stem cell transplant for CD5+ diffuse large-B cell lymphoma

CD5+ diffuse large B-cell lymphoma (DLBCL) is a rare subtype characterized by an inferior outcome. While dose-dense therapy shows promising activity, the optimal management remains to be determined. To evaluate the benefit of consolidative autologous hematopoietic stem cell transplantation (ASCT), we retrospectively reviewed the medical records of 47 consecutive patients with newly diagnosed de novo CD5+ DLBCL. Of 19 patients ≤ 70 of age with age-adjusted International Prognostic Index 2–3, eight underwent upfront ASCT, and nine did not, despite preserved organ function and response after induction therapy. The remaining two, ineligible for ASCT due to early progression or comorbidities, had a dismal clinical course. Among younger 17 high-risk patients eligible for ASCT, ASCT was associated with better overall (p = 0.0327) and progression-free survival (p = 0.0184). Younger patients without ASCT demonstrated similar outcomes to older patients with similar risk profiles. ASCT could be considered for high-risk CD5+ DLBCL with a response after induction therapy.

Clinical significance of bone marrow involvement by immunoglobulin gene rearrangement in de novo diffuse large B-cell lymphoma: a multicenter retrospective study.

Bone marrow (BM) involvement is an indicator of a poor prognosis in diffuse large B-cell lymphoma (DLBCL); however, few studies have evaluated the role of immunoglobulin gene rearrangement (IgR) in detecting BM involvement. We evaluated the clinical characteristics and treatment outcomes of patients with DLBCL based on histological BM involvement or positive BM IgR using polymerase chain reaction or next-generation sequencing. We also investigated the role of consolidative upfront autologous hematopoietic stem cell transplantation (ASCT) in patients with DLBCL and BM involvement. Among 624 patients, 123 (19.7%) with histological BM involvement and 88 (17.5%) with positive IgR in histologically negative BM had more advanced disease characteristics. Overall (OS) and progression-free (PFS) survival was better for patients with negative BM histology and negative IgR than that in patients with histological BM involvement (P = 0.050 and P < 0.001, respectively) and positive IgR with negative BM histology (P = 0.001 and P = 0.005, respectively). Survival rates did not differ among 82 (13.1%) patients who were treated with upfront ASCT and had histological BM involvement or positive IgR with negative BM histology. The survival outcomes were worse for patients who were not treated with upfront ASCT and for those with histological BM involvement or positive IgR, than for those with negative BM histology and negative IgR. Patients diagnosed with DLBCL and BM involvement based on histology or IgR had aggressive clinical features and poor survival. Upfront ASCT mitigated poor prognosis due to BM involvement.

Long-Term Responders after Upfront Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma

Long-Term Responders after Upfront Autologous Hematopoietic Stem Cell Transplant for Multiple Myeloma

Daratumumab-Based Maintenance in Patients with Relapsed Multiple Myeloma after Salvage Autologous Hematopoietic Stem Cell Transplantation

Introduction: Maintenance therapy is considered standard of care after upfront autologous hematopoietic stem cell transplantation (auto-HCT) for patients with newly diagnosed multiple myeloma (MM). However, there is paucity of data on the use of maintenance after a salvage auto-HCT, whether first or second. Aim: We designed a clinical trial for relapsed MM patients who underwent salvage auto-HCT after disease relapse to receive post-transplant maintenance with daratumumab (dara), with the addition of pomalidomide (pom) in a later amendment. Methods: We hypothesized that maintenance therapy with dara +/- pom will improve the progression-free survival (PFS) after a salvage auto-HCT. Patients with prior exposure to dara or pom were included, but patients refractory to either drug were excluded. The trial was planned to enroll a total of 56 patients. Patients received dara SQ weekly for weeks 1-8, every 2 weeks for weeks 9-24, and monthly from week 25 until progression. Pom was given at 2 mg PO from day 1-21 every 28 days. Patients received herpes zoster prophylaxis for the duration of the trial. The primary endpoint of this phase II trial was PFS. Disease response was assessed according to the International Myeloma Working Group (IMWG) uniform response criteria. Minimal residual disease (MRD) was measured by multiparametric flow cytometry (10 -5) in the bone marrow at day 90-180 after transplant. Results: The trial was terminated due to poor accrual after 13/56 patients were enrolled between May 2019 and August 2022. Median age at salvage auto-HCT was 64 (range: 43-76) years, and 7 patients (54%) were male. Median prior lines of treatment was 2 (range: 2-4). Six patients (46%) had a prior auto-HCT, and 7 (54%) had a hematopoietic stem cell comorbidity index (HCT-CI) of &amp;gt;3. Median time from diagnosis to salvage auto-HCT was 58.3 (range 7.6-132) months. Five patients (38%) had high-risk cytogenetic abnormalities (1q+ in all 5). Eight (61%) patients received melphalan alone, 4 (31%) received busulfan/melphalan, and 1 (8%) received gemcitabine/busulfan/melphalan/panobinostat as their conditioning regimen (Table 1). Three patients (23%) started maintenance with dara alone, while the remaining 10 (77%) patients received dara + pom. At study entry, 6 patients (46%) had a complete response (CR), 4 (31%) in very good partial response (VGPR), 2 (15%) in partial response (PR), and 1 (8%) had stable disease (SD). At day 100 post maintenance, 9 (69%) were in CR, while 1 (8%) each had VGPR, PR, SD and progressive disease (PD), respectively. For the 12 patients that did not progress at day 100, best response to dara +/- pom maintenance was CR in 10 (83%), and VGPR and SD in 1 (8%) each. With a median follow up of 26.1 months (range: 14.2-37.7) from the start of maintenance, 3 patients had progressed but there are no deaths so far. Median PFS from the date of auto-HCT was not reached, and from start of maintenance 28.5 (95% CI 26.3-NA) months. 2-year PFS was 92% (Figure 1). Most common adverse events were neutropenia (n=11, 84%; none grade&amp;gt;3), grade 1-2 fatigue (n=6, 46%), and grade ≤3 bacterial infection, grade ≤3 viral infection, grade 1-2 diarrhea and grade 1 thrombocytopenia (n=5, 38% each). Conclusion: Maintenance therapy with dara, with or without pom, is safe and feasible after a salvage auto-HCT for MM, with 83% achieving a CR. After a median follow up exceeding 2 years, the median PFS was 28.5 months. The trial was terminated due to poor accrual.

Impact of Revised International Staging System 2 (R2-ISS) Risk Stratification on Outcomes of Patients with Multiple Myeloma Receiving Autologous Hematopoietic Stem Cell Transplantation

Background: The second revision of the International Staging System (R2-ISS) is a new and simple tool to risk stratify newly diagnosed multiple myeloma (NDMM) patients. Our aim in this study was to evaluate the utility of R2-ISS in NDMM patients who received upfront autologous hematopoietic stem cell transplantation (auto-HCT). Methods: We conducted a retrospective analysis of all NDMM patients who underwent upfront auto-HCT between 1988 and 2021 at MD Anderson Cancer Center and had available data for calculation of R2-ISS, including albumin, β-2 microglobulin, LDH, and fluorescence in-situ hybridization (FISH) analysis at diagnosis. High-risk cytogenetic abnormalities (HRCA) were t(4;14), del(17p), and 1q21 gain or amplification, as detected by FISH. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was hematological response after auto-HCT. Results: A total of 1291 patients were included, with a median age of 62 years (range 29 - 83) and 60% were male. Four hundred-and-nineteen patients (32%) had HRCA. Most patients received either bortezomib, lenalidomide, and dexamethasone (VRD) (34%) or carfilzomib, lenalidomide, and dexamethasone (KRD) (25%) induction regimens, and most patients (95%) received melphalan based conditioning. The distribution of R2-ISS stages in our cohort was as follows: 123 (10%) stage I, 471 (36%) stage II, 566 (44%) stage III, and 131 (10%) stage IV. A total of 1027 (80%) patients received post auto-HCT maintenance, mostly lenalidomide with or without dexamethasone (n = 785, 61%) (Table 1). With a median follow-up of 42.2 months (range 0.3 - 181.0) for the entire cohort, the median PFS was 73.0, 65.2, 44.0, and 24.8 months ( P &amp;lt; .001) and the median OS was 130.8, 128.5, 94.2, and 61.4 months ( P &amp;lt; .001) for patients with R2-ISS stages I, II, III, and IV, respectively (Figure 1). On multivariable analysis (MVA) for PFS, using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (hazard ratio [95% CI], 1.11 [0.76-1.63]; P = .59), but there was a significant worsening in PFS for R2-ISS stage III (1.55 [1.05-2.29]; P = .028) and R2-ISS stage IV (2.04 [1.24-3.36]; P = .005). On MVA for OS, again using R2-ISS stage I as the reference group, there was no significant difference for R2-ISS stage II (1.33 [0.74-2.40]; P = .34) or R2-ISS stage III (1.75 [0.97-3.17]; P = .06), but there was a significant worsening in OS for R2-ISS stage IV (2.43 [1.18-5.01]; P = .017). On MVA, other measures significantly associated with worsening PFS were year of auto-HCT &amp;lt; 2010, lambda light chain disease subtype, presence of HRCA, prior MRD/response other than negative/≥CR, and not achieving MRD negative/≥ CR post auto-HCT. For OS, other measures significantly associated with worsening survival on MVA were presence of HRCA, HCT-CI &amp;gt; 3, having at least one bone lesion, not achieving CR at best response, and not receiving post auto-HCT maintenance therapy. Conclusion: Our study demonstrates that R2-ISS is a reliable prognostic tool for NDMM in a large cohort of patients who received standard anti-myeloma treatment, including modern induction regimens, upfront auto-HCT, and post-transplant maintenance.

Trends in Outcomes over Three Decades after Upfront Autologous Stem Cell Transplant for Multiple Myeloma at MD Anderson Cancer Center

Introduction Remarkable advances have been made in the treatment of multiple myeloma (MM) with the advent of novel therapies and the use of post-transplant maintenance. We report trends in outcomes of MM patients who received upfront autologous hematopoietic stem cell transplantation (autoHCT) at our institution over more than three decades. Methods We conducted a single-center retrospective study of patients with newly diagnosed MM undergoing upfront autoHCT between 1988 to 2021. Patients were grouped by the year of autoHCT: 1988-2000 (n=249), 2001-2005 (n=373), 2006-2010 (n=568), 2011-2015 (n=815) and 2016-2021 (n=1036). High-risk cytogenetic abnormalities were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and group differences were assessed using the log-rank test. Associations between demographic and clinical factors and survival outcomes were evaluated using Cox proportional hazards regression analysis. Results A total of 3041 patients were included in our analysis. Median age at autoHCT increased from 52 years (1988-2000) to 62 years (2016-2021), with only 1% of transplanted patients being ≥ 65 years of age in 1988-2000, compared to 38% in 2016-2021 (p&amp;lt;0.001). The proportion of African-American patients increased from 9% in 1988-2000 to 19% in 2016-2021 (p=0.004). The incidence of high-risk cytogenetics increased from 15% in 1988-2000 to 40% in 2016-2021 (p&amp;lt;0.001). The comorbidity burden, as measured by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), increased over time, with 17% of patients having HCT-CI&amp;gt;3 in 1988-2000 compared to 28% in 2016-2021 (p&amp;lt;0.001). Induction regimens evolved over time from predominately conventional chemotherapy (39%) in 1988-2000 to immunomodulatory drug (IMiD) and proteasome inhibitor (PI)-based regimens, with 74% receiving an IMiD-PI containing triplet [39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone (KRD)] between 2016-2021 (p&amp;lt;0.001). Maintenance therapy was used in &amp;gt;80% from 2011 onwards (Table 1). Response rates prior to autoHCT steadily improved with 4% and 10% patients achieving ≥CR and ≥VGPR between 1988-2000, compared to 19% and 65% between 2016-2021, respectively. At day 100 post-transplant, 24% and 49% patients achieved ≥CR and ≥VGPR between 1988-2000 compared to 41% and 81% between 2016-2021, respectively. At best post-transplant response, 33% and 53% patients achieved ≥CR and ≥VGPR between 1988-2000 compared to 63% and 91% between 2016-2021, respectively. The median PFS in the entire study population was 38.3 months (95% CI 36.4-40.3), improving from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (hazard ratio [95% CI]: 0.42 [0.36-0.50], p&amp;lt;0.001; Figure 1A). Notably, patients with high-risk cytogenetics also had an improvement in PFS in recent years, with a median PFS of 28.0 months (0.38 [0.26-0.55], p&amp;lt;0.001) and 36.8 months (0.32 [0.22-0.46], p&amp;lt;0.001) in 2011-2015 and 2016-2021, respectively, compared to only 13.7 months in 2001-2005. Patients aged ≥65 years also had an improvement in median PFS from 33.6 months (95% CI 23.1-44.2) between 2001-2005 to 52.8 months (95% CI 40.0-68.5, p&amp;lt;0.001) between 2016-2021. Median OS was 99.4 months (95% CI 94.2-104.0) in the entire study population, steadily improving from 55.1 months to not reached (0.41 [0.33-0.52], p&amp;lt;0.001) in 1988-2000 and 2016-2021, respectively (Figure 1B). Similarly, in those with high-risk cytogenetics, OS improved with a median OS of 32.9 months in 2001-2005 compared to 66.5 months (0.39 [0.26-0.61], p&amp;lt;0.001) in 2016-2021. Between 1988-2000, day 100 non-relapse mortality (NRM) was 6%, whereas from 2001 onwards NRM remained ≤ 1% (p&amp;lt;0.001). Conclusions This single-center analysis of over 3,000 newly diagnosed MM patients undergoing upfront autoHCT demonstrates significant improvements in the depth of response and survival outcomes over the past three decades, even in patients with high-risk disease. NRM remained &amp;lt;1% despite increasing age and comorbidity burden.

Effect of high-dose chemotherapy with upfront autologous hematopoietic stem cell transplantation on the prognosis of patients with stage IV diffuse large B-cell lymphoma.

Актуальность: Повышение эффективности первой линии терапии диффузной В-крупноклеточной лимфомы (ДВКЛ), особенно высокого риска, остается сложной и актуальной клинической задачей онкогематологии. Преимущество применения высокодозной химиотерапии с трансплантацией аутологичных гемопоэтических стволовых клеток (ВДХТ с ауто-ТГСК) в первой линии ДВКЛ с целью снижения риска развития рецидива и улучшения прогноза не определено и актуально для клинических исследований. Цель: изучение влияния ВДХТ с ауто-ТГСК в первой линии на прогноз у пациентов с IV стадией ДВКЛ. Материалы и методы: Ретроспективно проанализировано 105 пациентов, в возрасте 18-65 лет, с IV стадией ДВКЛ NOS, IPI ≥ 2, достигших ПО/ЧО (полного ответа/частичного ответа) после 6 курсов R-CHOP/R-DA-EPOCH. Пациенты получали лечение в ФГБУ «НМИЦ онкологии им. Н.Н. Петрова» Минздрава России с 2010 по 2019 годы. В группе ТГСК (n=35) проводилась ВДХТ с ауто-ТГСК в первой ремиссии. Группа контроля (n=70) находилась под наблюдением после 6 курсов иммунохимиотерапии (ИХТ) при достижении ПО. Первичные конечные точки – 1-годичная, 3-летняя безрецидивная выживаемость (БРВ), вторичная конечная точка – 3-летняя общая выживаемость (ОВ). Результаты: ВДХТ с ауто-ТГСК в первой линии продемонстрировала преимущество в показателях 1-годичной (р = 0,01) и 3-летней БРВ (р = 0,029), ОВ (р = 0,047). У пациентов с лимфомой с коэкспрессией myc, bcl-2 (double-expressor lymphoma, DEL) отмечено более значимое улучшение 1-годичной (р &lt;0,001) и 3-летней БРВ (р &lt;0,001), ОВ (р &lt;0,001) при проведении ВДХТ с ауто-ТГСК в первой линии. В группе ТГСК наличие DEL не влияло на 1-годичную (р = 0,44), 3-летнюю БРВ (р = 0,17) и ОВ (р = 0,34). Заключение: ВДХТ с ауто-ТГСК в первой линии улучшает прогноз у пациентов с IV стадией ДВКЛ, IPI ≥ 2. У пациентов с DEL позитивное влияние ВДХТ с ауто-ТГСК в первой линии на БРВ, ОВ выше. Неблагоприятное влияние DEL на прогноз нивелируется проведением ВДХТ с ауто-ТГСК в первой линии.

Lenalidomide Maintenance for Patients with Newly Diagnosed Multiple Myeloma Post Autologous Stem Cell Transplant: A Comparison of Real-World Treatment Outcomes and Costs

BACKGROUNDIn 2017, lenalidomide maintenance therapy (R-MT) was approved for patients (pts) who received an up-front autologous hematopoietic stem cell transplantation (ASCT) in the United States (US) and Europe. The total cost of care for pts on R-MT in the US has not been previously studied using a large administrative claims database. This study aimed to compare real-world outcomes and costs among pts with newly diagnosed multiple myeloma (MM) receiving R-MT vs no maintenance (No-MT) post ASCT.METHODSFrom the Truven Marketscan data set, we identified adult pts with ≥ 2 claims for MM (International Classification of Diseases, 9th/10th Revision, Clinical Modification code: 203.0x, C90.0x) 30 days apart and ≥ 1 MM treatment during the identification period (1/1/2011 to 9/30/2016). Pts were required to have continuous enrollment for 6 months pre and ≥ 6 months post initial ASCT date plus 90 days (index date), in addition to ≥ 1 full cycle of therapy with a valid first-line regimen, and evidence of ASCT during follow-up period. Patients were excluded if they had evidence of prior MM diagnosis or treatment. R-MT was defined as lenalidomide monotherapy of < 20 mg per day for ≥ 21 of 28 days. Treatment outcomes and healthcare costs during follow-up were compared among those initiating R-MT vs No-MT. Time to treatment discontinuation (TTTD) was defined as the duration from initiation of R-MT to discontinuation of R-MT. Time to next treatment (TTNT) was defined as the duration from the index date until the initiation of another second-line therapy. Kaplan-Meier (KM) and Cox proportional hazard models were performed to evaluate TTTD and TTNT. Per patient per month (PPPM) total healthcare costs were calculated at 12, 24, and 36 months among pts initiating R-MT or No-MT. Pharmacy costs included oral MM treatments and other oral medications. Outpatient costs were composed of IV medications and physician and ER visits, while hospitalizations were part of inpatient costs. Generalized linear regression models with negative binomial distribution and log link function were used to assess differences in PPPM while adjusting for differences in baseline characteristics.RESULTSA total of 250 and 233 pts initiated R-MT and No-MT, respectively. Mean age (58.5 vs 58.0 y, P= .5236) and Charlson Comorbidity Index score (5.2 vs 5.3, P= .5234) were similar, but there were more males in the No-MT group (52.0% vs 61.4%, P= .0378). Time from start of first-line regimen to ASCT (5.48 vs 5.47 months, P= .9589) and the mean follow-up time post index date (22.1 vs 21 months, P= .1414) were similar in both groups. R-MT pts had a median duration of maintenance of 10 months. The median TTTD using the KM method was 21.02 months (95% CI: 16.78, 25.76). During the study period, a total of 60 (24%) and 99 (42.5%) R-MT and No-MT pts received a second-line treatment. At 12, 24, and 36 months, the proportion of pts who had a second-line treatment was as follows: R-MT-12.4%, 21.2%, 22.8%; No-MT-35.2%, 40.3%, 42.1%. Median TTNT was significantly longer among those treated with R-MT vs No-MT (Figure 1). Adjusted total PPPM costs during the first 12 months of follow-up was higher among pts treated with R-MT vs No-MT ($13,095 vs $8,910, adjusted difference $4,514, P < .0001). Mean pharmacy PPPM costs were higher in R-MT pts ($8,603 vs $2,269, P < .0001) while outpatient costs were higher in the No-MT group ($3,761 vs $5,360, P < .0001), and inpatient costs were similar ($731 vs $1,281, P < .5076). The adjusted difference in total PPPM costs during 12-24 months of follow-up was $6,579, P < .0001. A similar cost trend was observed in months 24-36 of follow-up; however, even fewer patients had sufficient follow-up: Adjusted difference: $6,110, P= .0024.CONCLUSIONPts remain on R-MT for several months to well over a year. R-MT pts incurred higher costs within the study period; however, their TTNT was significantly longer, and they were over half as likely to progress to a second-line treatment compared with No-MT pts. Pharmacy costs in R-MT pts were higher in the initial year of follow-up while No-MT pts had higher outpatient costs, presumably driven by the need for second-line therapy in a higher proportion of patients. Additional follow-up is required to assess total healthcare costs in subsequent years. [Display omitted] DisclosuresHari:Celgene: Consultancy, Honoraria, Research Funding. Ung:Celgene Corporation: Other: Fellowship is funded by Celgene. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Ni:Celgene: Employment. Parikh:Celgene Corporation: Employment. Agarwal:Celgene Corporation: Employment.

Effective mobilization with etoposide and cyclophosphamide for collection of peripheral blood stem cell in patients with multiple myeloma

To evaluate the efficacy and toxicity of etoposide and cyclophosphamide for mobilization peripheral stem cells in multiple myeloma patients. We retrospectively analyzed 46 patients with multiple myeloma who underwent peripheral blood stem cell collection for upfront autologous hematopoietic stem cell transplantation in the First Affiliated Hospital of Xi'an Jiaotong University between January 2010 and July 2019. The mobilization protocols included cyclophosphamide 2.0 g/m2 with G-CSF (CTX group) before January 2015, and two-days of 5 mg/kg.d etoposide and 1.0 g/m2.d cyclophosphamide with G-CSF (EC group) after January 2015. The success rate of harvest (≥2×106 cells/kg) during the first mobilization attempt was 82.1% in the EC group and 50.0% in the CTX group, and the rate of adequate harvest (≥4×106 cells/kg) was 57.1% in the EC group and 15.8% in the CTX group. After the second mobilization, a sufficient number of CD34+/kg cells for an auto-HSCT was obtained for all patients in the EC group and the majority (68.4%) of patients in CTX group. There was no significant difference of non-hematological adverse events between two groups. The mean neutrophil engraftment time was 11.22±1.56 days and 9.89±2.81days for the CTX and EC groups, respectively (P>0.05). Platelet engraftments were significantly faster in the EC group than the CTX group (P0.05). The etoposide and cyclophosphamide regimen could be an effective and safe method for mobilization in patients with multiple myeloma.

Age no bar: A CIBMTR analysis of elderly patients undergoing autologous hematopoietic cell transplantation for multiple myeloma.

Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori. An increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2 . On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1-1.7 [P=.06]), REL (HR, 1.03; 99% CI, 0.9-1.1 [P=0.6]), PFS (HR, 1.06; 99% CI, 1-1.2 [P=0.2]), and OS (HR, 1.2; 99% CI, 1-1.4 [P=.02]) compared with the reference group (those aged 60-69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2 , including day 100 NRM (1% [95% CI, 1%-2%] vs 0% [95% CI, 0%-1%]; P=.003]), 2-year PFS (64% [95% CI, 60%-67%] vs 69% [95% CI, 66%-73%]; P=.003), and 2-year OS (85% [95% CI, 82%-87%] vs 89% [95% CI, 86%-91%]; P=.01]), likely representing frailty. The results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.

Upfront autologous hematopoietic stem cell transplantation for high-risk patients with double-expressor diffuse large B cell lymphoma.

Although MYC and BCL2 co-expression in diffuse large B cell lymphoma (DLBCL) is associated with inferior prognosis, it remains uncertain whether upfront autologous hematopoietic stem cell transplantation (ASCT) is beneficial in this lymphoma. This study aimed to investigate whether ASCT consolidation could have a positive role for patients with MYC and BCL2 co-expression (double-expressor lymphoma, DEL). We retrospectively evaluated 67 DLBCL patients who underwent upfront ASCT following rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy. The 5-year overall survival (OS) and progression-free survival (PFS) were 82.3% and 79.2%, respectively. There were 23 (34.3%) patients with DEL and 51 (76.1%) patients with non-germinal center B cell (GCB) subtype. The 5-year OS and PFS of patients with DEL were not different from those with non-DEL (P = 0.429 and P = 0.614, respectively). No survival difference for OS and PFS was also observed between GCB and non-GCB subtypes (P = 0.950 and P = 0.901, respectively). The OS and PFS were comparable for patients with DEL and non-DEL and both GCB and non-GCB subtypes. In conclusion, MYC and BCL2 co-expression did not have a poor prognostic impact among high-risk patients with DLBCL treated with upfront ASCT regardless of molecular classification. This preliminary study suggested that the role of consolidative ASCT is needed to be evaluated in a prospective randomized clinical trial.

Age Is a Prognostic Factor for the Overall Survival of Patients with Multiple Myeloma Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation.

In this retrospective analysis, we evaluated the impact of age on the outcome of patients with multiple myeloma who received an autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. A total of 1128 patients were divided into the older (>70 years; 182 [16%]) and the younger (≤70 years; 946 [84%]) groups. Compared with the younger cohort, older patients had a higher International Staging System (ISS) stage (ISS-II, 57 [31%] versus 215 [23%]; ISS-III, 52 [28%] versus 211 [22%]; P=.01), higher use of reduced-dose melphalan as a conditioning regimen (140 mg/m², 59 [32%] versus 29 [3%]; P < .001), and a higher comorbidity index (median, 3 versus 2; P=.01). Nonrelapse mortality at 1 year after auto-HCT was significantly higher in older patients (7 [4%] versus 9 [1%]; hazard ratio [HR], 4.1; P=.005). Complete remission rates after auto-HCT for the older and the younger groups were 41% and 46%, respectively. With a median follow-up of 52 months, the 5-year progression-free survival (PFS) was 24% (95% confidence interval [CI], 17% to 32%) and 37% (95% CI, 33% to 40%) in the older and younger groups, respectively (HR, 1.3; P=.02). Five-year OS for the older and younger groups was 56% (95% CI, 47% to 64%) and 73% (95% CI, 70% to 76%; P < .001), respectively. Older age emerged as one of the predictors of shorter OS but not PFS in the multivariate classification and regression tree analysis. In conclusion, age ≥70 years was associated with shorter PFS and OS in patients with multiple myeloma who underwent an auto-HCT.

Impact of Autologous Transplantation in Patients with Multiple Myeloma with t(11;14): A Propensity-Score Matched Analysis.

Patients with multiple myeloma with t(11;14) have been considered to have standard-risk disease. However, several recent reports have shown contradictory results. We identified 95 patients with multiple myeloma with t(11;14) on FISH studies, who underwent upfront autologous hematopoietic stem cell transplant (auto-HCT) at our center. We compared their outcome with a group of standard-risk patients with multiple myeloma who had diploid cytogenetics by both conventional cytogenetics (CC) and FISH (n = 287). To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis. A total of 160 patients, 80 in each group, were identified. Patients in the 2 groups were matched for age, International staging system stage at diagnosis, serum creatinine at presentation, disease status at auto-HCT, type of preparative regimens, dose of melphalan used for conditioning, and induction and maintenance regimens. Patients in t(11;14) group had a post auto-HCT overall response rate (ORR) of 97.5% (78/80), compared with 100% (80/80) in the standard-risk control group (P = 0.50). Complete response rate in the t(11;14) group was 35% (28/80), compared with 45% (36/80) in the standard-risk control group (P = 0.26). The 4-year PFS rates were 40.8% (95% CI, 29.6%-56.1%) and 51.1% (95% CI, 39.4%-66.3%) in the t(11;14) and standard-risk control groups, respectively (P = 0.14). The 4-year OS rates were 74.9% (95% CI, 63.3%-88.7%) and 88.3% (95% CI, 80.4%-97.0%) in the t(11;14) and standard-risk control groups, respectively (P = 0.17). Also, patients with t(11;14) with concurrent cytogenetics had significantly poor PFS and OS compared with a propensity matched standard-risk control group. Our study confirms that t(11;14) multiple myeloma undergoing upfront autologous transplantation had similar outcomes as patients with multiple myeloma with normal cytogenetic and FISH studies. Existence of additional genomic aberrations by CC or FISH was associated with a worse outcome.

Metaphase Cytogenetics for Risk Stratification in Newly Diagnosed Multiple Myeloma

Introduction: Abnormal metaphase cytogenetics are associated with inferior survival in newly diagnosed multiple myeloma (MM). These abnormalities are only detected in one third of cases due to the low proliferative rate of plasma cells. It is unknown if metaphase cytogenetics improve risk stratification when using contemporary prognostic models such as the revised international staging system (R-ISS), which incorporates interphase fluorescence in situ hybridization (FISH). Aims: The aims of this study were to 1) characterize the association between abnormalities on metaphase cytogenetics and overall survival (OS) in newly diagnosed MM treated with novel agents and 2) evaluate whether the addition of metaphase cytogenetics to R-ISS, age, and plasma cell labeling index (PCLI) improves model discrimination with respect to OS. Methods: We analyzed a retrospective cohort of 483 newly diagnosed MM patients treated with proteasome inhibitors (PI) and/or immunomodulators (IMID) who had metaphase cytogenetics performed prior to initiation of therapy. Abnormal metaphase cytogenetics were defined as MM specific abnormalities, while normal metaphase cytogenetics included constitutional cytogenetic variants, age-related Y chromosome loss, and normal metaphase karyotypes. Multivariable adjusted proportional hazards regression models were fit for the association between known prognostic factors and OS. Covariates associated with inferior OS on multivariable analysis included R-ISS stage, age ≥ 70, PCLI ≥ 2, and abnormal metaphase cytogenetics. We devised a risk scoring system weighted by their respective hazard ratios (R-ISS II +1, R-ISS III + 2, age ≥ 70 +2, PCLI ≥ 2 +1, metaphase cytogenetic abnormalities + 1). Low (LR), intermediate (IR), and high risk (HR) groups were established based on risk scores of 0-1, 2-3, and 4-5 in modeling without metaphase cytogenetics, and scores of 0-1, 2-3, and 4-6 in modeling incorporating metaphase cytogenetics, respectively. Survival estimates were calculated using the Kaplan-Meier method. Survival analysis was stratified by LR, IR, and HR groups in models 1) excluding metaphase cytogenetics 2) including metaphase cytogenetics and 3) including metaphase cytogenetics, with IR stratified by presence and absence of metaphase cytogenetic abnormalities. Survival estimates were compared between groups using the log-rank test. Harrell's C was used to compare the predictive power of risk modeling with and without metaphase cytogenetics. Results: Median age at diagnosis was 66 (31-95), 281 patients (58%) were men, median follow up was 5.5 years (0.04-14.4), and median OS was 6.4 years (95% CI 5.7-6.8). Ninety-seven patients (20%) were R-ISS stage I, 318 (66%) stage II, and 68 (14%) stage III. One-hundred and fourteen patients (24%) had high-risk abnormalities by FISH, and 115 (24%) had abnormal metaphase cytogenetics. Three-hundred and thirteen patients (65%) received an IMID, 119 (25%) a PI, 51 (10%) received IMID and PI, and 137 (28%) underwent upfront autologous hematopoietic stem cell transplantation (ASCT). On multivariable analysis, R-ISS (HR 1.59, 95% CI 1.29-1.97, p &lt; 0.001), age ≥ 70 (HR 2.32, 95% CI 1.83-2.93, p &lt; 0.001), PCLI ≥ 2, (HR 1.52, 95% CI 1.16-2.00, p=0.002) and abnormalities on metaphase cytogenetics (HR 1.35, 95% CI 1.05-1.75, p=0.019) were associated with inferior OS. IR and HR groups experienced significantly worse survival compared to LR groups in models excluding (Figure 1A) and including (Figure 1B) the effect of metaphase cytogenetics (p &lt; 0.001 for all comparisons). However, the inclusion of metaphase cytogenetics did not improve discrimination. Likewise, subgroup analysis of IR patients by the presence or absence of metaphase cytogenetic abnormalities did not improve risk stratification (Figure 1C) (p &lt; 0.001). The addition of metaphase cytogenetics to risk modeling with R-ISS stage, age ≥ 70, and PCLI ≥ 2 did not improve prognostic performance when evaluated by Harrell's C (c=0.636 without cytogenetics, c=0.642 with cytogenetics, absolute difference 0.005, 95% CI 0.002-0.012, p=0.142). Conclusions: Abnormalities on metaphase cytogenetics at diagnosis are associated with inferior OS in MM when accounting for the effects of R-ISS, age, and PCLI. However, the addition of metaphase cytogenetics to prognostic modeling incorporating these covariates did not significantly improve risk stratification. Disclosures Lacy: Celgene: Research Funding. Dispenzieri:Akcea: Consultancy; Intellia: Consultancy; Alnylam: Research Funding; Celgene: Research Funding; Janssen: Consultancy; Pfizer: Research Funding; Takeda: Research Funding. Kapoor:Celgene: Honoraria; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Amgen: Research Funding; Glaxo Smith Kline: Research Funding. Leung:Prothena: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Omeros: Research Funding; Aduro: Membership on an entity's Board of Directors or advisory committees. Kumar:Celgene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Takeda: Research Funding.

Upfront autologous hematopoietic stem cell transplantation consolidation for patients with aggressive B-cell lymphomas in first remission in the rituximab era: A systematic review and meta-analysis.

The outcomes for patients with diffuse large B-cell lymphoma (DLBCL) with adverse clinical prognostic factors such as a high age-adjusted International Prognostic Index (aaIPI) are not optimal. In the current study, the authors performed a systematic review and meta-analysis to assess the totality of evidence pertaining to the efficacy of autologous hematopoietic stem cell transplantation (auto-HCT) consolidation for patients with DLBCL in first remission. The authors searched the Cochrane and MEDLINE/PubMed databases through December 1, 2018, for studies comparing conventional chemotherapy with rituximab (R-chemo) versus R-chemo and auto-HCT. Two authors independently reviewed all references for study inclusion and extracted data related to benefits (overall survival, progression-free survival, and response rates) and harms (treatment-related mortality and adverse events). Four studies (1173 patients) met the inclusion criteria and were included in the current analysis. The median duration of follow-up ranged from 42 to 76months. There was no difference noted with regard to the overall survival (hazard ratio, 1.01; 95% CI, 0.74-1.37), progression-free survival (hazard ratio, 0.77; 95% CI, 0.58-1.04), or response rates (risk ratio, 0.98; 95% CI, 0.92-1.04) between patients who received R-chemo and auto-HCT and those who received R-chemo alone. The risk of mortality and therapy failure was not found to be different when the analysis was limited to high aaIPI between the 2 groups. Although there was no difference noted with regard to the risk of treatment-related mortality, there was a significantly higher incidence of CTCAEgrade 3 or 4 adverse events in patients who received R-chemo and auto-HCT compared with patients treated with R-chemo alone. The findings from what to the authors' knowledge is the first meta-analysis performed in the rituximab era demonstrated no beneficial effect of upfront auto-HCT consolidation in patients with aggressive B-cell non-Hodgkin lymphoma, including high-risk clinical groups (high aaIPI).

A Multi-Center Prospective Study of GLIDE Chemotherapy Consolidated with Autologous Stem Cell Transplantation for Patients with Newly Diagnosed Advanced-Stage or Relapsed Extranodal Natural Killer/T-Cell Lymphoma

Background: The prognosis of nasal type advanced-stage or relapsed extranodal NK/T cell lymphoma (ENKTL) is poor even with intensive multi-agent chemotherapy. It is therefore critical to develop more effective treatment strategies to improve outcomes and prognosis of ENKTL patients. Methods: We conducted a multi-center, prospective study to evaluate the efficacy and safety of a new treatment strategy: induction chemotherapy with gemcitabine, L-asparaginase or PEG-asparaginase, ifosfamide, dexamethasone and etoposide (GLIDE) followed by upfront autologous hematopoietic stem cell transplantation (ASCT) conditioning with either carmustine, etoposide, cytarabine, and melphalan (BEAM) or chidamide, cladribine, gemcitabine, and busulfan (ChiCGB). Findings: A total of 64 eligible patients were enrolled. After a maximum of 6 cycles of GLIDE, 43 patients (70·5%) achieved complete response, including 31 (50·8%) who achieved complete response after 2 cycles. With median follow-up of 23.8 months, estimated 5-year progression-free survival and overall survival of the whole cohort was 54·0% and 68.9% respectively. Among 50 chemo-sensitive patients (patients in complete or partial remission) , 27 underwent upfront ASCT, and they showed a significantly higher rate of 5-year progression-free survival than chemosensitive patients who did not receive upfront ASCT (78·8% vs. 36·0%, p=0·0004) as well as a significantly higher rate of 5-year overall survival (87·2% vs. 55·4%, p=0·0035). Interpretation: GLIDE chemotherapy showed a high efficacy in disease control for the patients with advance-staged or relapsed ENTKL, and in whom achieved partial or complete response, GLIDE followed by upfront ASCT may be a more effective treatment strategy than GLIDE alone. Trial Registration Information: The study was registered at the Chinese Clinical Trial Registry (Chictr.org.cn, Chicrt-TNC-10000782). Funding Statement: This work was supported by a grant from Science and Technology Fund of Sichuan Province, China, NO.18ZDYF2063. Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: This study was approved by the Ethics Committee of West China Hospital, Sichuan University. Written informed consent was obtained from all patients.

Upfront autologous hematopoietic stem cell transplantation in patients with high-risk stage III to IV Hodgkin lymphoma: a multicenter retrospective cohort study

ABSTRACTBackground/Objective: Nearly 30% of patients with advanced-stage Hodgkin lymphoma (HL) are not cured. We should better control tumors with initial treatment for patients with advanced stage HL whose interim positron emission tomography/computed tomography (PET/CT) was positive. The objective of our study was to confirm the superiority of autologous hematopoietic stem cell transplantation (ASCT) therapy in these patients.Methods: Eighty-nine HL patients with stage III-IV, international prognostic score (IPS) ≥3 and Deauville more than 3° at the interim PET/CT were analyzed. Forty five patients received ASCT. The other 44 patients received two cycles DHAP chemotherapy.Results: The 3-year overall survival (OS) of patients who received ASCT was 91.1%, and for the patients who received chemotherapy, it was 72.7% (P = 0.025). The 3-year progression free survival (PFS) of patients in the ASCT group was 88.9%, but for patients in the chemotherapy group, it was only 70.5%(P = 0.017). No patient died of toxicity from ASCT. Additionally, there was no difference in the rates of secondary malignancies between the ASCT and chemotherapy groups. Extranodal and bone marrow involvement were poor prognostic factors, while ASCT was a good prognostic factor.Conclusion: The use of ASCT as a first-line consolidation treatment could improve outcome of patients with advanced-stage high risk HL whose interim PET/CT was positive.

Characteristics and Outcome of Multiple Myeloma Patients Presenting with Anemia Only: a Retrospective Multi-Center Study

Background:Multiple myeloma (MM) is defined as bone marrow monoclonal plasmocytosis combined with either specific laboratory or imaging findings (SLIM criteria) or one or more of the following myeloma defining events (MDE) including anemia, hypercalcemia, renal failure or lytic bone lesions (CRAB criteria). Patients who presents with anemia but without additional CRAB criteria are scarce, and their clinical course has not yet been characterized in the literature.The current study was designed to evaluate the characteristics, responsiveness to treatment, progression free and overall survival in newly diagnosed MM patients presenting with anemia only.Methods:We retrospectively analyzed the clinical features and outcomes of MM patients that presented with anemia as the only CRAB criteria (i.e. having no evidence of skeletal involvement by PETCT, MRI or total body CT, no renal involvement and no hypercalcemia), that were diagnosed and treated in 9 Israeli and Greek centers between 2010 and 2018.Baseline characteristics at diagnosis, ISS score, treatment regimens, depth and duration of response (by IMWG criteria), hemoglobin (HB) levels during treatment and overall survival (OS) were collected and analyzed.Results: 63 (28 females) patients were included in the analysis. The median age was 72.2 (range 34.4-91.9) years. The median HB level at diagnosis was 9.4 g/l (IQR 6.0-12.0) and median platelets level was 172000 (IQR 59000-454000). The median percent of plasma cells (PCs) in bone marrow at diagnosis was 60% (range 20% to 99%). 11 out of 56 (19%) patients had a high-risk FISH (t 4;14, t 14;16 or del 17p). Bortezomib -based induction was administered in 83%, and upfront autologous hematopoietic stem cell transplantation (autoHCT) was employed in 32%.ORR to 1st line was 87%. 37 (62%) achieved ≥ VGPR, 16 (25%) PR and 7 (13%) SD/PD. Significant predictors for achieving at least VGPR vs. SD or PD were higher albumin level at diagnosis (3.9±0.5 g/l vs. 3.5±0.4g/l, p<0.00), maximal HB level during treatment (13.0±1.0g/l vs. 11.5±1.2 g/l respectively, p<0.00) and maximal improvement in HB level during treatment (median 3.2 [IQR 2.2-4.5]g/l vs 2.2 [IQR 1.1-3.2]g/l, respectively, p<0.00).Median PFS in the entire cohort was 22.1±5.82 months. Predictors for PFS duration on first-line therapy were bone marrow plasmocytosis (HR 1.012 [95% CI 1.001-1.037] p=0.03) and maximal improvement in hemoglobin level (HR 0.71 [95% CI 0.55-0.91] p< 0.00). Multivariate analysis confirmed bone marrow plasmocytosis (HR 1.03 [95% CI 1.01-1.05], p<0.00), higher HB level at diagnosis (HR 0.43 [95% CI 0.27-0.67], p<0.00) and maximal improvement in HB level during therapy (HR 0.37 [95% CI 0.25-0.56] p<0.00) to be associated with longer PFS. In multivariate analysis restricted to non-transplanted patients, factors associated with longer PFS were bone marrow plasmocytosis>60% (HR 4.6 [95% CI 1.5-14.0] p<0.00), HB level at diagnosis (HR 0.32 [95% CI 0.17-0.60], p<0.00), maximal HB improvement (HR 0.23 [95% CI 0.13-0.41] p<0.00) and older age (HR 0.92 [95% CI 0.87-0.97], p<0.00).Within a median follow-up of 34 months, 19 (31%) patients have died; 12 due to PD. The median OS for the entire cohort was 65.93 months and the 3 years mortality rate was 17.5%.Predictors of mortality were high risk cytogenetics (HR 3.01 [95% CI 1.02-8.88] p= 0.04), maximal HB improvement during therapy (HR 0.73, [95% CI 0.54-0.99] p=0.04), and bone marrow plasmocytosis (HR 1.04 [95% CI 1.01 to 1.07] p= 0<.00). Furthermore, median OS for patients <60% plasmocytosis was not reached, compared to 45.3 months for patients with plasmocytosis ≥60% (p=0.048) (figure 1). Only bone marrow plasmocytosis remained as significant factor for mortality in a multivariate analysis (HR 1.04 [95% CI 1.01-1.08], p=0.01).Conclusion:MM patients presenting with anemia only, often have a remarkable bone marrow plasmocytosisResponsiveness to therapy, PFS and OS, depend on the degree of BM plasmocytosis and HB level at diagnosis, both reflecting disease burden. In line with that, response to therapy and long -term PFS can be accurately predicted by the degree of improvement in HB level.In general , patients presenting with anemia only , although they do not have renal impairment or bone disease, seem to have a relatively poor OS of approximately 5 years only , suggesting that these patients may have a relatively “rapidly growing tumor”, precluding the development of bone and renal disease. DisclosuresNo relevant conflicts of interest to declare.

Older Age As a Prognostic Factor for Overall Survival for Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Stem Cell Transplantation

BackgroundHigh-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) is considered the standard of care for newly diagnosed, transplant-eligible multiple myeloma (MM) patients. Due to improvements in induction, stem cell mobilization, and dose adjustment of the conditioning regimen, auto-HCT is increasingly used in older MM patients, with several retrospective analyses showing similar clinical outcomes compared to younger patients.MethodsTo further confirm these results, we performed a single-center retrospective analysis of MM patients undergoing auto-HCT between January 2006 and December 2016. Patients were divided into two groups: older (> 70 years) and younger (≤ 70 years).Results1128 patients (182 older, 946 younger) were included in this analysis. Patient characteristics are summarized in the attached Table. More patients (59% vs. 45%, p = 0.01) in the older cohort had ISS stage II or III disease. Older cohort was more likely to receive reduced-dose melphalan (140 mg/m²) as conditioning regimen (32% vs 3%, p = <0.0001). There was no significant difference in high-risk cytogenetics, induction regimens, and response to induction, or post-transplant maintenance between the older and younger cohorts. The overall median follow-up among survivors was 49 months in the older and 52 months in the younger group. One-hundred-day non-relapse mortality (NRM) was 2/182 (1.1%) and 6/946 (0.6%) (p = 0.5) in the older and younger groups, respectively. However, 1-year NRM was significantly higher in the older vs. younger cohort (7 /182 (4%; unknown 3, pneumonia or respiratory failure 4) vs. 9/946 (1%; unknown 2, pneumonia or respiratory failure 4, cardiac failure 3), HR 4.1, p = 0.005). Post-transplant, 75 (41%) and 431 (45%) achieved complete remission (CR) in the older and younger groups, respectively (p = 0.29). There was no significant difference in the rate of disease progression post-transplant between older (31%) and younger (30%) groups (p = 0.3). The 5-year progression free survival (PFS) was 24% and 37% in the older and younger groups, respectively (HR 1.3, p = 0.02). Similarly, 5-year overall survival (OS) was 56% and 73% in the older and younger groups (HR 1.8, p = <0.001). In univariate analyses, age > 70 years, high-risk cytogenetics, serum creatinine level > 2 mg/dl and ISS stage III were associated with worse PFS and OS. In contrast, melphalan 200 mg/m² for conditioning and achievement of CR after induction therapy were associated with better PFS and OS. These 6 factors were studied in multivariate analyses using a classification and regression tree (CART) method. In CART analysis for PFS, ISS stage II or III, and high-risk cytogenetics were associated with shorter PFS. Similarly, in CART analysis for OS, older age (> 69 years), ISS stage II or III, and high-risk cytogenetics were associated with a shorter OS.ConclusionIn this large single-center analysis, there was no difference in 100-day NRM, CR rates and the risk of progression after auto-HCT between the older and the younger patients. However, older age was associated with a shorter PFS and OS due to increased NRM. On multivariate CART analysis, ISS stage II or III and high-risk cytogenetics were associated with a worse PFS and OS, while age > 69 years was associated with a worse OS only. The impact of comorbidities on NRM is being evaluated in ongoing analyses. [Display omitted] DisclosuresLee:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies Corporation: Consultancy; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Chugai Biopharmaceuticals: Consultancy; Takeda Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Patel:Abbvie: Research Funding; Takeda: Research Funding; Poseida Therapeutics, Inc.: Research Funding; Celgene: Research Funding. Thomas:Bristol Myers Squibb Inc.: Research Funding; Celgene: Research Funding; Acerta Pharma: Research Funding; Amgen Inc: Research Funding; Array Pharma: Research Funding. Orlowski:BioTheryX, Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Poseida: Research Funding; Bristol Myers Squibb: Consultancy; Genentech: Consultancy; Millenium Pharmaceuticals: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Melphalan-Based Autologous Transplantation in the Octogenarian Multiple Myeloma Patient Population

Abstract:Background:Upfront autologous hematopoietic stem cell transplantation (auto-HCT) combined with novel anti-myeloma drugs is considered the standard of care for transplant-eligible patients with multiple myeloma (MM). However, this treatment is generally avoided in older patients due to concerns about toxicity. MM is primarily a disease of the elderly, with >35% patients being older than 70 years of age at diagnosis. We have previously reported on the role of auto-HCT in MM patients >70 years1. In this study, we evaluate the safety and feasibility of auto-HCT in patients ≥80 years who received auto-HCT at our institution.Methods:We retrospectively reviewed the outcomes of MM patients with age ≥80 years who underwent auto-HCT between January, 2007, and June, 2018. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of auto-HCT to the last follow up or the censored date. Kaplan-Meier method was used to estimate PFS and OS.Results:Between January, 2013, and December, 2017, out of a total of 1465 MM patients referred for evaluation for auto-HCT at our institution, only 10(0.68%) were of age ≥80 years. Also, between January, 2016, and June, 2018, a total of 210 MM patients with age ≥80 years were treated at our institution, and only 3(0.14%) underwent auto-HCT. Overall among 1740 patients with MM who received an auto-HCT at our institution between the beginning of 2007 to June, 2018, 9(0.5%) patients were ≥ 80 years of age (range 80-83). Table 1 summarizes the patient characteristics of these nine patients. All patients had an ECOG performance status of either 0 or 1. The median hematopoietic stem cell transplant - comorbidity index for the cohort was 3 (range, 0-5). Eight (89%) patients were in first remission, and 1 (11%) patient had relapsed disease at auto-HCT. All patients received melphalan at a reduced dose of 140 mg/m2 as the conditioning regimen. Eight patients (89%) received maintenance therapy with lenalidomide. The median follow-up from auto-HCT was 18 months (range 0.5 - 50 months). No (0%) patient died within 100 days of auto-HCT. Out of 8 evaluable patients, 4 (50%) achieved a complete response, 2 (25%) very-good partial, and 2 (25%) achieved a partial response with an overall response rate of 100%. Eight (89%) patients were alive until the last follow-up. Median PFS was 31.5 months, while the median OS has not been reached (Fig1). 2-yr PFS and OS were 62.5% and 75% respectively. One patient died 22 months post-transplant due to non-transplant related cause.Conclusions:In selected MM patients ≥80 years old, auto-HCT was feasible, with 0% TRM, 100% response rate, and 2-year OS of 75%. Almost 90% of these patients went on to receive maintenance therapy.