scholarly journals Impact of Daratumumab on Stem Cell Collection, Graft Composition and Engraftment Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplant

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 35-37
Author(s):  
Shivaprasad Manjappa ◽  
Robert Fox ◽  
Jane Reese ◽  
Amin Firoozamand ◽  
Hannah Schmikla ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Treated Group ◽  
Advisory Board ◽  
P Value ◽  
Platelet Recovery ◽  
Colony Forming Unit ◽  
Stem Cell Collection ◽  
Graft Composition

Background High dose chemotherapy followed by autologous stem cell transplantation (ASCT) plays an important role in the treatment of transplant-eligible multiple myeloma (MM) patients and yields deep responses, prolongs progression-free survival (PFS) and overall survival (OS). Daratumumab (Dara), a humanized monoclonal antibody that binds to CD38+ on the surface of myeloma cells and is increasingly used upfront to treat MM. Up to 75% of mobilized CD34+ hematopoietic progenitors also express CD38 and, hence exposure to Dara may potentially impact stem cell mobilization, and, given the extended half-life of Dara, also impair engraftment. The Cassiopeia trial (Moreau, P. 2019) showed the utility of Dara in combination with bortezomib and thalidomide as upfront treatment for MM without a negative impact on stem cell collection yield. Similarly, the Griffin trial (Voorhees, PM, 2020) demonstrated the safety of upfront Dara when combined with bortezomib and lenalidomide also with no impact on stem cell collection or engraftment. However, others(Al Saleh, A. 2019) reported delayed neutrophil engraftment in patients treated with Dara. Given the conflicting findings of these studies and scarcity of data on the direct impact of Dara on erythroid and myeloid progenitors, we investigated the effect of Dara on stem cell collection yield, graft composition and time to engraftment among patients who underwent ASCT. Methods We evaluated all patients with MM who underwent ASCT at our institute between 2017-2020 and excluded patients undergoing 2nd transplant or tandem ASCT. Disease risk stratification was assessed as per International Staging System (ISS) for MM. Treatment response prior to transplant was assessed as per response criteria definitions by International Myeloma Working Group (IMWG). Stem cells were collected according to institutional protocol and prior to cryopreservation, 1x105 peripheral blood cells are plated in duplicate in semi-solid media- MethoCult™ H4434 (Stem Cell Technologies, Vancouver, BC) and cultured in 37°C, 5% CO2 following which CFU-GM (colony forming unit- granulocyte macrophage) and BFU-E (burst forming units- erythroid) colonies are scored on day 14 based on morphological recognition, and reported as 104 colonies per kg of recipient weight. CFU-C (colony forming unit combined) is calculated by combining BFU-E and CFU-GM. Results Patients (N=108) that underwent ASCT between 2017-2020 were identified and demographic data are summarized (Table 1). Sixteen patients received Dara as part of upfront treatment prior to stem cell collection. Median age was 62 years old for the entire group with no significant age difference between patients who received Dara vs. those who did not receive. Similarly, there was no difference in race, ISS stage, pre-transplant response, plerixafor or lenalidomide use between the groups. Pts who received Dara were more likely to have received more than one chemotherapy regimen prior to transplant (62.5% vs. 30%, p-value=0.014). Although, total and day 1 collection of CD34+ stem cells was lower in the Dara treated group (7.18 x 106/kg) compared to Dara untreated (8.78 x 106/kg), the difference was not statistically significant. (p-value=0.151). Stem cell product composition based on measurement of BFU-E, CFU-GM and CFU-C colonies were similar independent of Dara use. Prior exposure to Dara was also not predictive of day 1 stem cell collection failure (defined as < 5x106 CD34+ cells/kg) as determined by multivariate analysis. Median time to absolute neutrophil count (ANC) recovery (defined as ANC >1500) was 12 days in both groups (p-value=0.09). Median time to platelet recovery (defined as platelet count >20k) was 12 days in the Darauntreated group vs. 13 days Dara treated group (p-value=0.06). Discussion In this single institute experience, there was a trend towards lower CD34+ collection as well as lower progenitor scoring with Dara use but was not statistically significant and also there was no difference in time to ANC or platelet recovery. The majority of patients in this study received plerixafor for mobilization, which might abrogate the effect of Dara and lenalidomide on the graft and stem cell collection. Further studies to investigate the impact of Dara on CD38+ mobilized hematopoietic cells is warranted. Disclosures Manjappa: Pfizer: Research Funding. Caimi:Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Verastem: Other: Advisory Board; Celgene: Speakers Bureau; Kite pharmaceuticals: Other: Advisory Board; ADC therapeutics: Other: Advisory Board, Research Funding. de Lima:BMS: Other: Personal Fees, advisory board; Incyte: Other: Personal Fees, advisory board; Kadmon: Other: Personal Fees, Advisory board; Celgene: Research Funding; Pfizer: Other: Personal fees, advisory board, Research Funding. Malek:Clegene: Other: Advisory board , Speakers Bureau; Janssen: Other: Advisory board, Speakers Bureau; Sanofi: Other: Advisory board; Amgen: Honoraria; Medpacto: Research Funding; Cumberland: Research Funding; Bluespark: Research Funding; Takeda: Other: Advisory board , Speakers Bureau.

A Comparison of Chemotherapy + G-CSF Versus Plerixafor (Mozobil®) + G-CSF for Stem Cell Mobilization In Patients with Multiple Myeloma Treated with Lenalidomide

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2258-2258
Author(s):  
Tomer M Mark ◽  
Adriana C Rossi ◽  
Roger N Pearse ◽  
Morton Coleman ◽  
David Bernstein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Cell Yield ◽  
High Dose ◽  
Advisory Committees ◽  
Cd34 Cells ◽  
Stem Cell Collection

Abstract Abstract 2258 Background: Prior use of lenalidomide beyond 6 cycles of therapy in the treatment of multiple myeloma (MM) has been shown to negatively impact stem cell yield, but this phenomenon can be overcome with the addition of high-dose cyclophosphamide to standard G-CSF mobilization. We hypothesized that the use of plerixafor (Mozobil®) would compare similarly to chemotherapy in rescuing the ability to collect stem cells in lenalidomide-treated myeloma. Methods: We performed a retrospective study comparing the efficacy of plerixafor + G-CSF mobilization (PG) to chemotherapy + G-CSF (CG) (either high-dose cyclophosphamide at 3g/m2 or DCEP [4-day infusional dexamethasone/ cyclophosphamide/ etoposide/cisplatin]) in 49 consecutive stem cell collection attempts in patients with MM exposed to prior lenalidomide. The primary endpoint was the ability to collect sufficient stem cells for at least two transplants (minimum 5×106 CD34+ cells/kg), comparing results in terms of total exposure to lenalidomide and time elapsed from lenalidomide exposure until the mobilization attempt. The secondary endpoint was number of apheresis days required to meet collection goal. Resilts: Twenty-four patients underwent PG mobilization and twenty-five with CG (21 with G-CSF + cyclophosphamide, 4 with G-CSF+DCEP). The two groups did not differ in terms of total amount of lenalidomide exposure: median number of lenalidomide cycles for patients mobilized with PG was 6.5 (range 1.2–86.6), vs. 6 (range 2–21.6), for patients mobilized with CG (P = 0.663). The median time between mobilization and last lenalidomide dose was also similar between the two groups: 57.5 (range 12–462) days for PG vs. 154 (range 27–805) days for CG (P = 0.101). There was an equivalent rate of successful collection of 100% for PG and 96% for CG, P = 0.322. One patient failed collection in the CG group due to emergent hospitalization for septic shock during a period of neutropenia; no patient collected with PG had a serious adverse event that interrupted the collection process. Stem cell yield did not differ between the two arms (13.9 vs. 18.8 × 106 million CD34+ cells/kg for PG vs. CG respectively, P = 0.083). Average time to collection goal was also equal, with a median of time of 1 day required in both groups, (range 1–2 days for PG, 1–5 days for CG, P = 0.073). There was no relationship between amount of lenalidomide exposure and stem cell yield with either PG (P = 0.243) or CG (P = 0.867). Conclusion: A plerixafor + G-CSF mobilization schedule is equivalent in efficacy to chemotherapy + G-CSF in obtaining adequate numbers of stem cells for two autologous stem cell transplants in patients with MM exposed to lenalidomide; however, PG may be a less toxic approach than chemomobilization. Number of lenalidomide cycles has no impact on chances of stem cell collection success using either method. Disclosures: Mark: Celgene Corp: Speakers Bureau; Millenium Corp: Speakers Bureau. Zafar: Celgene Corp: Speakers Bureau. Niesvizky: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Consultancy, Research Funding.

Phase II Trial of Intravenously Administered AMD3100 (Plerixafor) for Stem Cell Mobilization in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation Following a Lenalidomide-Based Initial Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2992-2992
Author(s):  
Shaji Kumar ◽  
Joseph R. Mikhael ◽  
Martha Q Lacy ◽  
Betsy R. LaPlant ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Adverse Events ◽  
Research Funding ◽  
Maximum Yield ◽  
Early Morning ◽  
Initial Therapy ◽  
Cd34 Cells ◽  
Rate Of Failure ◽  
Stem Cell Collection

Abstract Abstract 2992 Background: Patients with myeloma receiving initial therapy with lenalidomide-based regimens can have difficulty collecting adequate stem cells for an autologous transplant. Stem cell collection in these patients can be significantly enhanced by addition of the CXCR-4 antagonist plerixafor to the mobilization regimen. Plerixafor is typically given subcutaneously (SQ), with collection approximately 11 hours after injection to obtain maximum yield. Intravenous administration can potentially allow more rapid and predictable mobilization compared to the SQ route. We designed this trial to prospectively assess the efficacy of intravenous plerixafor administration in patients undergoing lenalidomide therapy. Patients and methods: Patients who were receiving initial therapy with a lenalidomide-based regimen and were undergoing stem cell collection within 12 months of their myeloma diagnosis were enrolled. Patients received GCSF at 10 μg/kg/day for 4 days followed by addition of plerixafor at 0.24 mg/kg/dose starting on day 5. Plerixafor was administered intravenously early morning (6–7 am) followed by apheresis beginning 4–5 hours later. Plerixafor was administered for a maximum of 4 days; but patients could continue apheresis beyond the 4th day at treating physician discretion. The aims of the study were to determine the proportion of patients reaching a stem cell yield of at least 3 million CD34 cells/kg by second day of apheresis, the safety and tolerability of intravenously administered plerixafor, and the overall rate of failure to mobilize (defined as less than 2.5 million CD34 cells/kg in 4 collections). Results: Thirty-seven patients were accrued between December 2009 – April 2011, and 36 were eligible for analysis. The median age was 61 years (range; 28–73); 61% were male. The median time from start of initial therapy to enrollment was 4.6 months (range; 2.6 to 11.1) and the median cycles of lenalidomide were 4 (range; 3–11). Thirty-four (94%) of the patients achieved at least 3 million CD34 cells/kg within 2 days of apheresis. The median CD34 cells/kg after 1 day of collection was 3.9 million (range; 0.7 to 9.2) and after two days of collection was 7.02 million (range: 1.1–16.5). Two patients failed the mobilization (<2.5 million CD34 cells/kg). There were no grade 3 or 4 non-hematological adverse events and one patient experienced grade 4 thrombocytopenia. The most common grade 1 or 2 adverse events seen were gastrointestinal, namely nausea, diarrhea and abdominal pain or bloating. Grade 1 dizziness was reported in 8 patients. Overall, the infusion was well tolerated. Conclusion: Intravenously administered plerixafor is an effective strategy for mobilization in this patient group with low rate of failure to mobilize. It is well tolerated with toxicity comparable to the SQ administration. It also offers flexibility in patient scheduling with a convenient schedule for early morning infusion followed by apheresis later in the day. Disclosures: Kumar: Merck: Consultancy, Honoraria; Celgene: Consultancy, Research Funding; Millennium Pharmaceuticals, Inc.: Research Funding; Genzyme: Research Funding; Novartis: Research Funding. Off Label Use: Use of the investigational agent MLN9708 for the treatment of previously untreated multiple myeloma. Lacy:Celgene: Research Funding.

scholarly journals Impact of Daratumumab-Containing Induction on Stem Cell Mobilization and Collection, Engraftment and Hospitalization Parameters Among Multiple Myeloma Patients Undergoing Autologous Stem Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3886-3886
Author(s):  
Evangelos Eleutherakis Papaiakovou ◽  
Evangelos Terpos ◽  
Nikolaos Kanellias ◽  
Magdalini Migkou ◽  
Maria Gavriatopoulou ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Treated Group ◽  
High Dose ◽  
On Demand ◽  
Increased Risk

Abstract Introduction: Advances in induction regimens have significantly improved depth of response and duration of remission in multiple myeloma (MM) patients who are eligible for high-dose therapy and autologous stem cell transplantation (ASCT). Proteasome inhibitor-based induction regimens are standard as part of induction and it has been shown not to have any detrimental effect on stem cell (SC) collection and engraftment. Daratumumab (DARA) is an IgG1k monoclonal antibody directed against CD38 with potent antimyeloma activity. Based on the results of prospective studies DARA is now approved as part of induction therapy. Available data indicate a potential impact of DARA on SC collection but there is limited data on engraftment, duration of hospitalization and infection risk. In this retrospective analysis we evaluated the effect of DARA-based induction on ASCT parameters. Methods: The analysis included consecutive newly diagnosed MM patients that received ASCT between 2016 and 2020, as part of their upfront treatment regimen in our institution (Department of Clinical Therapeutics, Athens, Greece). Per institutional protocol, after 4-6 cycles of induction, pts received low dose cyclophosphamide (2.5 g/m2) followed by G-CSF (10 mcg/Kg/day) to mobilize and collect SCs. Plerixafor was administered on-demand in case of poor mobilization and insufficient first day collection. Large volume leukapheresis was performed in pts with low CD34+ counts in order to increase CD34+ yield. Pts received G-CSF 480 μcg once daily from day +4 after SC reinfusion to ANC &gt;1500/mm3. All pts received antiviral and antifungal but no anti-bacterial prophylaxis. Results: 200 eligible pts were included in the analysis; 40 (20%) pts received DARA as part of PI-based upfront treatment and 160 (80%) pts received PI-based upfront treatment without DARA. Baseline demographics (age, gender, performance status) and disease characteristics (ISS and R-ISS stage, cytopenias, eGFR, lytic bone disease etc) were not different between the two groups. Response after induction was also similar (CR+VGPR rate was 93% vs 95% for non-DARA and DARA-containing regimens respectively). Use of DARA at induction was associated with lower total mean number of collected CD 34+ SCs (10.48 x 10^6/kg vs 16.58 x 10^6/kg, p&lt;0.0001), or SC collection on day 1 (7.99 x 10^6/kg vs 16.27 x 10^6/kg, p&lt;0.0001). Fewer pts in the DARA-treated group achieved the planned yield of at least 5 X 10^6 CD34+/kg, compared to DARA-untreated group (87.5 % vs 96.2%, p=0.047). DARA-treated pts required more often additional SC mobilization with on demand administration of plerixafor (42.5% vs 7.6%, p&lt;0.0001). In order to compensate for a poorer mobilization and lower quality graft (CD34% 0.66% vs 1.26% in apheresis product, p&lt;0.0001) DARA-treated group underwent more often &gt;1 day of SC collection (37.5% vs 6.3%, P &lt;0.0001), resulting in longer duration of collections (689 vs 452 min, p&lt;0.0001) and larger total apheresis volumes (723 vs 557 ml, p&lt;0.0001). However, 97% and 98% of pts in the two groups respectively were able to move to at least a single ASCT. Following ASCT, DARA-treated pts had a slightly delayed hematopoietic recovery (11 vs 10 days to PMN&gt;500/mm3, p&lt;0.001 and 12 vs 11 days for PLT counts&gt; 25x10^9/mm3, p&lt;0.001) and required more transfusions (2 vs 1 for RBCs, p=0.031 and 4 vs 2 for platelets, p&lt;0.001). Rates of neutropenic fever were higher (80% vs 67%, p=0.182), required antibiotics for longer duration (10 vs 8 days, p=0.042) and more often 2 or more lines of antibiotic therapy (53% vs 39%, p=0.003), experienced more often septic shock (12.5% vs 1.3%, p=0.003) and as a results DARA-treated pts had a slightly prolonged hospitalization (21 vs 19 days, p=0.02). However, D100 mortality was not statistically different (&lt;2% in both groups). Conclusion: DARA-containing induction before ASCT is associated with poorer mobilization and frequent need for use of plerixafor. However, similar percentage of patients can move to at least a single ASCT. The use of DARA-containing induction was also associated with slightly increased risk of infectious complications, antibiotics use and blood product transfusions but no increase in the risk of D100 mortality. These data point to the need for certain modifications to ASCT protocol for patients treated with DARA-containing regimens at induction, such as preemptive use of plerixafor, and perhaps prophylactic antibiotics. Disclosures Terpos: Amgen: Consultancy, Honoraria, Research Funding; BMS: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genesis: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; GSK: Honoraria, Research Funding. Gavriatopoulou: Takeda: Honoraria; Karyopharm: Honoraria; Sanofi: Honoraria; GSK: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Amgen: Honoraria. Dimopoulos: Amgen: Honoraria; BMS: Honoraria; Janssen: Honoraria; Takeda: Honoraria; BeiGene: Honoraria. Kastritis: Takeda: Honoraria; Pfizer: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Genesis Pharma: Honoraria; Janssen: Consultancy, Honoraria, Research Funding.

scholarly journals Vinorelbine-Cyclophosphamide Compared to Cyclophosphamide in Peripheral Blood Stem Cell Mobilization for Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3103-3103
Author(s):  
Sanjay De Mel ◽  
Yunxin Chen ◽  
Adeline Lin ◽  
Eng Soo Yap ◽  
Teck Guan Soh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Blood ◽  
P Value ◽  
High Dose ◽  
Haematopoietic Progenitor Cell ◽  
Cd 34 ◽  
Transfusion Requirements ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Background High dose therapy (HDT) followed by autologous stem cell rescue is the standard of care for transplant eligible patients with multiple myeloma (MM). High dose cyclophosphamide (Cy) at 4-7g/m2 with granulocyte colony stimulating factor (GCSF) has been shown to be effective for haematopoietic progenitor cell (HPC) mobilization despite associated haematologic toxicity.Vinorelbine 25mg/m2 in combination with Cy 1500mg/m2 (Vino-Cy) was shown to be comparable to Cy mobilization in a study using historical controls. Vino-Cy is the mobilization regimen of choice at the National University Hospital Singapore (NUH) while Cy mobilization is preferred at the Singapore General Hospital (SGH). We present a retrospective comparison of HPC mobilisation outcomes using Vino- Cy and Cy at these institutions. Methods Medical records for patients undergoing HPC mobilization between 2004 and 2014 at NUH and SGH were analysed. Patients mobilized with Vino -cy received Vinorelbine 25mg/m2 on day 1 followed by cyclophosphamide 1500mg/m2 on day 2, GCSF 10mcg/kg/day was given from day 4 onwards. Alternatively, pegylated GCSF 6mg was given on day 4. Patients mobilized with Cy were given cyclophosphamide 1500mg/m2 on day 1 and 2 and GCSF 10mcg/kg/day from day 5 onwards. Apheresis (using the cobe spectra or optia system at NUH and the Haemonetics MCS+ system at SGH) was commenced once a peripheral blood CD 34+ count of >/= 10 x 10 6/l was achieved. The number of total blood volume exchanges per apheresis was 3 at NUH and 4 at SGH. Apheresis was continued until a minimum target CD 34 collection of 5 x 10 6 per kg/BW was reached. Patients who were successfully mobilized proceeded to HDT with melphalan 200mg/m2. Results 133patients underwent HPC mobilization between 2004 and 2014. The median weight was 62 Kg for Vino Cy and 58Kg for the Cy patients (p=0.03). The groups were evenly matched in terms of age, presence of renal impairment, bone lesions, ISS stage and the use of novel agent based induction. Bortezomib based induction was used in 73% of Vino-Cy and 43% of Cy patients. A higher percentage of Cy patients were mobilized in complete remission (53%) compared to Vino-Cy (21%). Table 1 summarises the mobilization outcomes of the two groups. Although the total CD 34+ collection was greater in the Cy group, the difference in the percentage of patients achieving an adequate HPC collection was not statistically significant, 72/84 (85%) of Vino-Cy patients and 45/47 (95%) of Cy patients achieved a stem cell collection of greater than 5 x 10 6/Kg BW (P=0.07). There were two mobilization failures in each group, one of whom (a Vino-Cy patient) was previously treated with melphalan. The number of days taken to achieve an adequate peripheral blood HPC count was shorter in the Vino Cy group and the date of harvest was also more predictable for Vino Cy with a standard deviation of 0.95 compared to 1.95 for Cy. Grade 3-4 harvest related complications were significantly more common in the Cy group (table 2). There was no significant drop in haemoglobin after harvest in either group. Discussion Our data suggest that HPC mobilization maybe more effective with Cy, differing from data published by Annunziata et al which showed a superior HPC mobilization with Vino-Cy compared to the historical Cy control. Vino-Cy appears superior in terms of the time taken for an adequate peripheral CD34+ count and predictability of the day of harvest. The incidence of harvest related complications is also greater for Cy. These findings are common to our cohort and that reported by Annunziata et al. Data on transfusion requirements, hospitalization rates and survival are being collected. Prospective clinical trials are required to definitively determine which protocol is superior. Table 1. Day of protocol when harvest took place P value Number of days taken to harvest P value CD34+/Kg Collected P value Vino-Cy(n=84) Cy(n=47) Vino-Cy(n=84) Cy(n=47) Vino-Cy(n=84) Cy(n=47) Median 9 13 P=0.000 2 2 P=0.97 8.4 11.3 P=0.009 Mean 8.5 12 2 2 10.0 16.2 Maximum 11 16 5 5 32.5 73.9 Minimum 5 7 1 1 2.2 2.4 SD 0.95 1.9 0.94 0.93 5.7 14.5 Table1. Comparison of Mobilisation Outcomes with Vino-Cy and Cy. Table 2. Mobilisation Chemotherapy P value. Vino-Cy(84) Cyclophosphamide (47) Complications during and after harvest (grade3-4) 2(2.3) 9(19) 0.009 Fluid Overload 1 0 Neutropaenic Fever 1 8 Line related thrombosis 0 1 Table 2. Grade 3-4 Complications during and after stem cell collection, data presented as number (%). Disclosures No relevant conflicts of interest to declare.

scholarly journals Patient, Disease and Treatment Characteristics of Long-Term Survivors of Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2019-2019
Author(s):  
Michael Kennah ◽  
Nastaran Noroozi ◽  
Esther Masih-Khan ◽  
Tony Panzarella ◽  
Donna E Reece ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Novel Agents ◽  
P Value ◽  
Prolonged Therapy ◽  
Disease Characteristics ◽  
Treatment Characteristics ◽  
Long Term Survivors

Abstract Introduction With routine use of autologous stem cell transplantation (ASCT) and novel agents, survival of patients with multiple myeloma (MM) has improved in recent years. Yet, MM remains incurable and long-term survivors (LTS) of ≥10 years from diagnosis remain uncommon. This study aims to identify patient, disease and treatment characteristics of MM LTS, with particular interest in the effect of novel therapies. Methods A retrospective analysis was conducted of MM patients diagnosed between 1998 and 2002 and treated at Princess Margaret Cancer Centre, a tertiary care institution. LTS were identified by survival of ≥10 years from diagnosis and were compared with patients diagnosed and followed contemporaneously at our institution with survival <10 years from diagnosis. Candidate predictor variables were identified using univariate and multivariate logistic regression analysis; a p value <0.05 was considered statistically significant. Results Seventy-five patients were identified as LTS, with a control group of 119 patients with survival <10 years. The median survival for all patients was 7.3 years (range 0.6-14.5 years). Comparison of patient, disease and treatment characteristics between groups are detailed in Table 1. Patient and disease characteristics: At diagnosis, LTS were younger (p = 0.0005) and at earlier ISS stage (p = 0.02) than non-LTS. At diagnosis, LTS had a higher baseline mean hemoglobin level (p = 0.02) and platelet count (p = 0.003), and less frequently had lytic bone lesions (p = 0.03), consistent with earlier stage at diagnosis. There were no significant differences in baseline mean leukocyte count, serum calcium and creatinine. Cytogenetics were not routinely performed during this time period. Treatment characteristics: Of the LTS, 95% received an ASCT, as compared to 86% of non-LTS (p = 0.77). Median age at transplant was younger in the LTS (p = 0.003). LTS experienced a longer time from transplant to disease progression (TTP) than non-LTS (p < 0.0001) despite achieving similar rates of complete response (CR) and very good partial response (VGPR). Exposure to novel agents was common in both the LTS and control groups (73% vs. 82%, p = 0.24). Length of exposure to thalidomide (p = 0.01) and lenalidomide (p = 0.002) was greater in LTS, leading to higher quality responses and longer TTP with both agents (p < 0.0001 and p = 0.002, respectively). Similarly, bortezomib exposure was longer in the LTS (p = 0.02) with a longer TTP over that achieved in non-LTS (p = 0.008), although the quality of response was not significantly different. In a multivariate analysis, a longer TTP after ASCT (OR = 1.004; 95% CI 1.002-1.006, p = 0.0008), thalidomide (OR = 34; 95% CI 1.7-690.6; p = 0.023) and bortezomib (OR = 28.2; 95% CI 3.5-228; p = 0.002) treatment, though not after lenalidomide, were independently predictive of LTS. Table 1. Comparison of characteristics between LTS and non-LTS Disease characteristics LTS (n=75) Non-LTS (n=119) p -value Age (y) 53.2 59.1 0.0005 ISS stage I 66 43 0.02 II 20 33 III 14 24 Hemoglobin (g/L) 109 102 0.03 Leukocytes (x 109/L) 5.97 6.29 0.45 Platelets (x 109/L) 255 218 0.003 Calcium (mmol/L) 2.41 2.46 0.39 Creatinine (umol/L) 107.5 148.6 0.16 Presence of lytic lesions (%) 55 70 0.03 Treatment characteristics Autologous stem cell transplant Age (median, years) 53.3 59.4 0.003 Response (CR or VGPR, %) 47 44 0.62 TTP (median, months) 59 19.9 0.001 Thalidomide Age (median, years) 11.4 8.2 0.01 Response (CR or VGPR, %) 40 23 0.02 TTP (median, months) 32.4 9.6 <0.0001 Lenalidomide Age (median, years) 23.2 8.1 0.002 Response (CR or VGPR, %) 56 35 0.04 TTP (median, months) 24 10.8 0.002 Bortezomib Age (median, years) 6.8 3.3 0.02 Response (CR or VGPR, %) 40 28 0.24 TTP (median, months) 18 6 0.008 Conclusion LTS with MM received prolonged therapy and achieved higher quality responses to both transplant and novel agents. Our analysis suggests that LTS have baseline characteristics (age, early-stage disease, greater marrow reserve) that may enable them to tolerate more intensive or prolonged therapy. However, it is possible that LTS have disease more indolent or sensitive to therapeutic interventions. The retrospective nature of the study limits our ability to further characterize this. Regardless, these data suggest that the practice of continued exposure to novel agents may contribute to long-term survival in MM. Disclosures Reece: Otsuka: Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Millennium: Honoraria, Research Funding; Merck: Research Funding; BMS: Research Funding; Novartis: Honoraria, Research Funding; Amgen: Honoraria. Trudel:Celgene: Honoraria; Novartis: Honoraria; Glaxo Smith Kline: Honoraria, Research Funding; Oncoethix: Research Funding. Kukreti:Celgene: Consultancy, Honoraria. Tiedemann:Janssen: Honoraria. Chen:Celgene: Honoraria; Janssen: Honoraria.

scholarly journals Autologous Stem Cell Transplantation for Multiple Myeloma Patients Aged ≥ 75 Treated with Novel Agents

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-13
Author(s):  
Iuliana Vaxman ◽  
Alissa Visram ◽  
Shaji K. Kumar ◽  
Angela Dispenzieri ◽  
Francis K. Buadi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Mayo Clinic ◽  
Research Funding ◽  
Advisory Board ◽  
Novel Agents

Introduction Autologous stem cell transplantation (ASCT) has been used for treating multiple myeloma (MM) for over three decades and is generally reserved for patients younger than 65 years of age. The definition of transplant eligible is ill-defined and different centers have different policies to determine which patients are transplant eligible. Some centers have an age cut-off, others use clinical judgment, and some use various frailty scores (a scoring system based on comorbidities and physical and cognitive assessments) aiming to objectively assess transplant eligibility. There are limited data about outcomes in patients ≥ 75 years. Aim To report on outcomes of ASCT in a cohort of patients with MM aged 75 years or older. Methods Retrospective study of all consecutive MM patients aged ≥ 75 years that underwent ASCT at Mayo Clinic, Rochester, Minnesota. Stem cell transplantation at our center is routinely performed as an outpatient, with patients being hospitalized when deemed clinically necessary upon physician review. Results Between October 2005 and March 2020, 46 patients aged 75 years or older, received an ASCT at Mayo Clinic, Rochester. The median hematopoietic stem cell transplantation specific comorbidity index (HCT-CI) was 0 (range 0-6) with 8 patients having HCT-CI of 5 or 6. Median time from diagnosis to ASCT was 6.45 months (IQR 5.2-10.52) and 54% received reduced intensity conditioning with melphalan 140 mg/m2. All patients except one (that was treated with dexamethasone only) received induction with novel agents (listed in table 1) and 6 patients (13%) received doublet induction. All others received triplet induction. 46% of patients completed the ASCT without requiring hospitalization and 54% (n=25) of patients required hospitalization with a median duration of hospital admission of 9 days (IQR 5-13). Reasons for hospitalization included fever or infection (32%), cardiac arrhythmia (36%) and dehydration (32%). Overall response rate was 100% with a complete response seen in 57% of patients and 16 patients achieving MRD negative sCR. Median overall survival and progression free survival for the cohort were 82 months and 33 months, respectively. One patient died within 100 days of transplant representing a 2% 100-day mortality rate. Univariable cox regression model that evaluated the effect of gender, high risk cytogenetics, hemoglobin, renal function and melphalan dose did not detect any variable that was predictive of OS or PFS (Table 3). Conclusions ASCT is efficacious and can be safely delivered in the outpatient setting in carefully screened patients aged 75 or above. An arbitrary cutoff for age should not be used to exclude patients from ASCT, rather a careful assessment of "physiological age" including performance status and co-morbidities is required by an experienced treating team. Disclosures Kumar: Amgen: Consultancy, Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments, Research Funding; Cellectar: Other; Carsgen: Other, Research Funding; Dr. Reddy's Laboratories: Honoraria; Genentech/Roche: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Sanofi: Research Funding; Kite Pharma: Consultancy, Research Funding; Novartis: Research Funding; Celgene/BMS: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Merck: Consultancy, Research Funding; MedImmune: Research Funding; BMS: Consultancy, Research Funding; Tenebio: Other, Research Funding; Karyopharm: Consultancy; AbbVie: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Janssen Oncology: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Takeda: Other: Research funding for clinical trials to the institution, Consulting/Advisory Board participation with no personal payments; Genecentrix: Consultancy; Oncopeptides: Consultancy, Other: Independent Review Committee; IRC member; Adaptive Biotechnologies: Consultancy. Dispenzieri:Pfizer: Research Funding; Janssen: Research Funding; Alnylam: Research Funding; Intellia: Research Funding; Takeda: Research Funding; Celgene: Research Funding. Dingli:Bristol Myers Squibb: Research Funding; Rigel: Consultancy; Janssen: Consultancy; Alexion: Consultancy; Karyopharm Therapeutics: Research Funding; Apellis: Consultancy; Sanofi-Genzyme: Consultancy; Millenium: Consultancy. Kapoor:Cellectar: Consultancy; Takeda: Honoraria, Research Funding; Celgene: Honoraria; Amgen: Research Funding; Sanofi: Consultancy, Research Funding; Janssen: Research Funding; GlaxoSmithKline: Research Funding. Gertz:Prothena: Other: personal fee; Medscape: Other: personal fee, Speakers Bureau; Appellis: Other: personal fee; Alnylam: Other: personal fee; Ionis/Akcea: Other: personal fee; Janssen: Other: personal fee; Research to Practice: Other; Sanofi: Other; Teva: Speakers Bureau; Johnson and Johnson: Speakers Bureau; DAVA oncology: Speakers Bureau; Proclara: Other; Springer Publishing: Patents & Royalties; Celgene: Other; Physicians Education Resource: Other: personal fee; Aurora Bio: Other; Amgen: Other: personal fee; Annexon: Other: personal fee; Spectrum: Other: personal fee, Research Funding; Abbvie: Other.

High-Dose Carfilzomib and Dexamethasone As First-Line Treatment in Symptomatic Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4258-4258 ◽  
Author(s):  
Tomer M Mark ◽  
Sujitha Yadlapati ◽  
Lyubov Neglyad ◽  
Jennifer Bourke ◽  
David Jayabalan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Maximum Response ◽  
First Line ◽  
Disease Response ◽  
First Line Therapy ◽  
Line Therapy ◽  
Grade 3 ◽  
Stem Cell Collection

Abstract Background: Carfilzomib (Cfz) is approved for use in relapsed and refractory multiple myeloma (RRMM) at a dose of 27mg/m2 after escalation from 20mg/m2. The response rate for Cfz and dexamethasone (dex) as first-line therapy in multiple myeloma (MM) is unknown. Higher doses of Cfz have been shown to enhance overall response in RRMM (Lendvai 2014); the presence of a dose-response relationship of Cfz for first-line therapy in untreated MM has not been evaluated. A protocol of Cfz-Dex induction at two dosing levels, followed by BiRd (Clarithromycin 500mg PO BID, Lenalidomide (Len) 25mg for 21/28 days, Dex 40mg weekly) consolidation, and thereafter Len (10mg 12/28 days) maintenance, evaluated response and safety by Cfz dose level in patients (pts) with newly diagnosed symptomatic MM. The ORR and safety data for Cfz-Dex induction stratified by Cfz dose is reported. Methods: 70 patients with untreated MM were enrolled in a phase 2 study of Cfz-dex. Cfz-dex is: Cfz IV on D1, 2, 8, 9, 15, 16 of a 28-day cycle at a dose of 20mg/m2 on days 1, 2 of cycle 1 and 45mg/m2 thereafter and Dex 40mg on D1, 8, 15, 22. After the first 26 pts were enrolled, the protocol was amended to increase the Cfz from 45 to 56mg/m2. Screening echocardiogram and pulmonary function testing were performed. Brain natriuretic peptide (BNP) was measured with each cycle. Cfz-dex was continued until plateau in disease response (unchanged M-protein for 2 cycles). Elective stem cell collection was then performed in transplant eligible pts. This was followed by BiRd until 2nd response plateau, and then by LEN maintenance. Disease response evaluation was performed monthly with serum and urine protein electrophoresis, immunofixation, and free light chain analysis; bone marrow biopsy with skeletal imaging was used to confirm MM progression or complete response (CR). Cytogenetic testing was performed on CD138-selected cells. Results: 25 pts received Cfz-Dex at 45 mg/m2 and 44 (out of 45 enrolled) pts at 56 mg/m2 for at least 1 cycle and were evaluable for response. 56% of pts were ISS II/III and 64% had high-risk cytogenetics as per IMWG definition. Pts received a median of 5 cycles of Cfz-dex in both the 45 mg/m2 (range 1-10) and 56 mg/m2 groups (range 1-14). Maximum response to Cfz-dex is shown in Table 1. There was no difference in response between the 45 and 56mg/m2 groups (P = 0.20). Median time to PR and maximum response for the 45 and 56 mg/m2 cohorts were both 2 and 3 cycles, respectively. 42 pts had stem cell harvest. All collected stem cells to support at least two transplants (> 5 x 10^6 CD34/kg) in one mobilization attempt using G-CSF, with mean yield of 13.74x10^6 CD34/kg (range 5.94-32.14). 79% collected in 1 apheresis session. Adverse events (AEs) were notable for renal failure in 3 pts (2 Grade 2, 1 grade 3) and congestive heart failure in 1 pt (grade 3). Two of the 3 cases of renal failure occurred in the 56 mg/m2 cohort, all other AEs occurred in the 45mg/m2 cohort. All AEs resolved after stopping Cfz. There was no correlation with TTE, PFTs or serial BNPs and development of cardiac or pulmonary toxicity. Discussion: This is the first prospective study evaluating induction responses to Cfz-dex in MM. Cfz-dex is safe and active in induction at both 45 and 56 mg/m2, with an ORR of 93% and rate of >= VGPR of 68% despite a primarily high risk population. Specific dose did not correlate with response. Higher dose of Cfz did not lead to more toxicity. Cfz-dex induction led to successful stem cell collection in all attempts. Cfz-dex is a highly active and well-tolerated induction regimen. Transitioning to IMiD-based therapy after maximum response led to deeper responses with a remarkable 97% rate of VGPR or better. Table 1. Maximum Response with Cfz-Dex, followed by BiRD consolidation and lenalidomide maintenance: Response Category Cfz-Dex 45 mg/m2 Cfz-Dex 56 mg/m2 Overall Cfz-Dex phase BiRD phase Lenalidomide maintenance phase N = 25 (%) N = 44 (%) N = 69 (%) N = 44 (%) N = 33 (%) >= PR 22 (88) 42 (95) 65 (93) 44 (100) 33 (100) >= VGPR 16 (72) 31 (70) 45 (68) 42 (95) 32 (97) >= CR 3 (12) 2 (5) 5 (7) 12 (27) 15 (45) SCR 3 (12) 2 (5) 5 (7) 9 (20) 13 (39) CR 0 (0) 0 (0) 0 (0) 3 (7) 2 (6) VGPR 13 (52) 29 (66) 42 (61) 30 (68) 17 (52) PR 6 (24) 11 (25) 17 (25) 2 (5) 1 (3) SD 3 (12) 2 (5) 5 (7) 0 0 Disclosures Mark: Calgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Off Label Use: Carfilzomib as first line therapy in myeloma.. Rossi:Amgen: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Pearse:Celegen: Consultancy. Perry:Takeda: Speakers Bureau; Celgene: Speakers Bureau. Pekle:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Huang:Celgene: Research Funding. Coleman:Celgene: Speakers Bureau; Takeda: Speakers Bureau. Chen-Kiang:Celgene: Consultancy. Niesvizky:Celgene: Consultancy, Speakers Bureau.

scholarly journals Effect of Daratumumab-Containing Induction on CD34+ Hematopoietic Stem Cells before Autologous Stem Cell Transplantation in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2764-2764
Author(s):  
Ondrej Venglar ◽  
Tereza Sevcikova ◽  
Anjana Anilkumar Sithara ◽  
Veronika Kapustova ◽  
Jan Vrana ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
Hematopoietic Stem ◽  
Platelet Recovery ◽  
Cd34 Cells ◽  
Fcm Analysis ◽  
D 12

Abstract Introduction: Daratumumab (Dara) is an anti-CD38 monoclonal antibody representing a novel treatment agent for multiple myeloma (MM). Nonetheless, several studies have reported a Dara-related impairment of CD34+ hematopoietic stem cell (HSC) mobilization and post-autologous stem cell transplantation (ASCT) complications, including low yields of mobilized HSCs and delayed neutrophil engraftment. Impact of Dara on the mobilization process and HSCs remains poorly understood even though sufficient yields of CD34+ cells are necessary for a successful ASCT and subsequent patient recovery. Aims: To compare the effect of the Dara-containing (Dara-Bortezomib-Dexamethasone [D-VCd]) and conventional (Bortezomib-Thalidomide-Dexamethasone [VTd]) therapy on CD34+ HSCs. Methods: Transplant eligible MM patients were treated with D-VCd or VTd induction regimen followed by a cyclophosphamide + G-CSF mobilization and a high-dose melphalan D -1 before ASCT. Flow cytometry (FCM) screening of CD34+ subsets was performed in the bone marrow (BM) or apheresis product (AP) at three consecutive time points: 1) diagnostic BM (DG), 2) mobilization AP (MOB), 3) a day prior ASCT BM (D-1). Furthermore, RNA sequencing (RNAseq) of sorted CD34+ cells was performed on total RNA with ribo-depletion protocol in AP after the induction. D-VCd samples had lower RNA yields thus the D-VCd or VTd groups were processed as independent batches. Results: Clinical data revealed no significant differences in mobilization (p &gt;0.050) likely due to a small cohort sizes (D-VCd n=5 vs VTd n=9), though a trend towards worse performance in D-VCd was observed. Median CD34+ cell yield was 3.08 vs 10.56 x 10 6/kg. Platelet recovery of &gt;20x10 9/L was D+14 vs D+12 (range: 11-18 vs 10-16). Neutrophil recovery of &gt;0.5x10 9/L was D+12 in both groups (range: 11-17 vs 11-12). In FCM analysis, DG (n=14), MOB D-VCd (n=5) vs VTd (n=9), D-1 D-VCd (n=7) vs VTd (n=15) were compared. CD34+ frequency (Fig. 1A) difference in MOB D-VCd vs VTd was insignificant (median: 1.15% vs 1.89%), whereas CD34+ fraction dropped in D-1 D-VCd (median: 0.52% vs 0.72%, p=0.027), albeit there was no significant reduction in D-1 D-VCd vs initial DG (median: 0.52% vs 0.45%). Differences in the distribution of certain HSC subsets were detected in the CD34+ pool (Fig. 1B-E). Frequency of multipotent progenitors (MPPs) (Fig. 1B) was increased in MOB D-VCd (median: 82.1% vs 66.2%, p=0.004). Frequency of lympho-myeloid-primed progenitor + granulocyte-monocyte progenitor (LMPP+GMP) (Fig. 1C) subset was reduced in D-VCd in both MOB (median: 1.7% vs 16.9%, p=0.042) and D-1 (median: 5.3% vs 14.0%; p=0.026). Erythro-myeloid progenitors (EMPs) (Fig. 1D) were reduced in MOB D-VCd (median: 10.7% vs 19.5%, p=0.042), while the frequency of EMPs increased in D-1 D-VCd (median: 20.8% vs 12.4%, p=0.045). No considerable differences were found in the expression of adhesion molecules CD44/HCAM or CD184/CXCR4. CD38 was strongly diminished in the whole D-VCd CD34+ fraction of MOB and D-1. To understand whether the differences in the mobilization efficacy after D-VCd induction were reflected in the expression profile of mobilized CD34+ cells, differential expression analysis was performed. Overall 133 significantly deregulated genes (p&lt;0.05; log fold change &gt;(-)1) between cohorts (D-VCd n=5 vs VTd n=5) were revealed (Fig. 2). Pathway analysis showed cellular response and localization as the most deregulated categories. The list of deregulated genes contained 25% of non-coding RNAs, some of which were linked to a protein localization in the cell (RN7SL1/2). The expression of adhesion molecules was inspected independently. Out of 59 HSC hallmark genes, only 8 were significantly altered in D-VCd. Interestingly, the main homing molecule CXCR4 seemed to be downregulated in D-VCd, while integrins A3 and B4 were upregulated. Conclusions: Despite the limited cohort sizes, a prospective trend of delayed neutrophil and platelet recovery was observed after D-VCd therapy. FCM analysis revealed a significant reduction of CD34+ subsets responsible, among others, for a reconstitution of neutrophils and megakaryocytes. A strong signal in transcriptome data which would potentially explain differential mobilization in D-VCd cohort was not detected, nevertheless, several genes with adhesive/homing and stem cell differentiation function were indeed altered. The results warrant further investigation. Figure 1 Figure 1. Disclosures Hajek: BMS: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharma MAR: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Impact of Neurocognitive Dysfunction in a Veteran Population Undergoing First Outpatient Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5883-5883
Author(s):  
Shakira J. Grant ◽  
Lindsay M. Hannan ◽  
Jessica L. Brand ◽  
Robert E. Richard ◽  
Daniel Y. Wu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Cognitive Impairment ◽  
Daily Living ◽  
Research Funding ◽  
Stem Cell Transplant ◽  
P Value ◽  
Cell Transplant ◽  
Neurocognitive Dysfunction ◽  
Hematopoietic Stem

INTRODUCTION Older adults (age > 70 years) with multiple myeloma (MM) are at higher risk of early mortality partly due to age-related factors, including impairments of cognition and function. To date, few studies have investigated the prevalence of neurocognitive impairment prior to autologous hematopoietic stem cell transplantation (ASCT) and its impact on post-transplant outcomes. We hypothesize, for patients with MM undergoing first outpatient ASCT, age >70 years or the presence of comorbid neurocognitive dysfunction decreases the time to first unplanned hospitalization occurring within 30 days post ASCT, and increases the overall length of stay (LOS) on the transplant service. METHODS We conducted a retrospective cohort study of 76 consecutive patients who underwent first ASCT at the Puget Sound Veterans Health Administration, for MM between January 2017 and December 2018. Patients with the following were excluded: amyloidosis, anaplastic plasmacytoma, and POEMS. Comprehensive psychological evaluations performed within 30 days prior to ASCT included: cognitive screening [Montreal Cognitive Assessment (MOCA)], depression [Patient Health Questionnaire-9 (PHQ-9)], and anxiety [General Anxiety Disorder- 7 (GAD-7)]. Functional status was assessed by activities of daily living (ADLS) and instrumental activities of daily living (IADLS). Data sources for table 1, included the institutional stem cell transplant database, and comprehensive electronic medical record review for each patient. This included vital status as of 7/15/19. Total LOS on the transplant service was measured as the time from arrival until discharge post-engraftment. For eligible patients, all portions of ASCT, including, stem cell collection, conditioning and stem cell infusion were completed as an outpatient. Statistical analyses were performed using SAS version 9.4. Kaplan Meier curves were generated to explore the association of cognitive scores and 1) time until first unplanned hospitalization within 30 days post-ASCT and 2) outpatient LOS on the stem cell transplant service. RESULTS Of the 76 patients undergoing ASCT, median age was 67 (range 40-79), 29% (22/76) were ≥ 70 years old . 67% (51/76) underwent ASCT within 1 year from diagnosis. The majority (73/76) scored ≥ 70 on a provider-assessed Karnofsky performance scale. Of those with MOCA scores available (n=64), impairments in cognition ranged from suspected mild cognitive impairment (MOCA 20-25) to probable cognitive impairment (MOCA 15-19), in 50% (32/64) and 6%( 8/64) of patients respectively. Those with MOCA scores< 26 were more likely to have ≥ 1 IADL impairment compared to those with scores ≥ 26 (Fisher Exact p=0.014). A total of 19 patients underwent planned hospitalization for conditioning followed by stem cell rescue, and therefore were not included in our analysis of unplanned hospitalization. Of the 57% (33/59) of patients with an unplanned inpatient admission within 30 days post-ASCT, the median time to first admission was 11 days. A total of 61% (17/28) and 53%(10/19) patients with MOCA <26 and ≥26, respectively, required hospitalization post-ASCT (log-rank p-value=0.70). There was no difference in the time to first unplanned hospitalization by age (<70, ≥70 years; log-rank p-value 0.58). Median time spent on the transplant service was 78 days (range 30 - 118). Suspected cognitive impairment did not influence time on the outpatient transplant service (median: 79 days MOCA <26 and 77 days MOCA ≥ 26, log-rank p-value=0.38). Median number of days on the transplant service differed by age group (log-rank p-value=0.02),) 76 vs 79 days in those age <70 and ≥70 respectively. CONCLUSION We found a high prevalence of cognitive impairment in MM patients undergoing first ASCT. However, we found no significant association between cognitive impairment or age and 30-day unplanned hospitalization. Older age (>70 years) was associated with a longer transplant service LOS. Thus, select older patients may have higher utilization of hospital resources post-ASCT compared to their younger counterparts. However confounding variables and selection bias may have influenced these preliminary results and additional analyses are ongoing. Future studies will evaluate the impact of age and pre-transplant neurocognitive function on additional outcomes, including longitudinal neurocognitive deterioration and impact on long-term morbidity and mortality. Disclosures Graf: TG Therapeutics: Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding.

Collection of Stem Cell Early In the Disease Course of Multiple Myeloma Is Associated with Early Engraftment.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4518-4518
Author(s):  
Francis Buadi ◽  
Angela Dispenzieri ◽  
Shaji Kumar ◽  
Martha Lacy ◽  
David Dingli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Research Funding ◽  
Complete Response ◽  
Cell Transplant ◽  
Disease Course ◽  
And Storage ◽  
Stem Cell Collection

Abstract Abstract 4518 Introduction: Autologous stem cell transplant (PBSCT) is an integral part of the management of Multiple Myeloma (MM). Available data suggest that the timing of PBSCT has no effect on overall outcome. Some patients currently opt to delay their transplant, especially in this era of proteosome inhibitors and iMIDs. In such patients the best time for stem cell collection is unknown. We conducted a retrospective study looking at early stem collection and storage compared to stem cell collection at the time of transplant in patients who opt to be transplanted at a later date. Method: All patients who had PBSCT performed more than one year from the time of diagnosis were reviewed. Two groups of interest were then evaluated. Early collection (ET): those who had stem cells collected within 6 months of diagnosis, and Late collection (LT): those who had stem cells collected more than 1 year from diagnosis and within 3 months of PBSCT. Results: Table 1 shows some patient characteristics. 334 patients were identified, ET (85) and LT (249). Gender distribution, Durie Salmon stage, immunoglobulin subtype and cytogenetic abnormalities were similar in both groups. The LT group was older 60 yrs compared to ET 56.6 yrs, P=0.02. More patients in the ET (77%) group were mobilized with cyclophosphamide compared to LT (51%) p<0.0001. Stem cell yield was similar in both groups 9.26 × 10(6) CD34/kg in ET and 8.19 × 10(6) in LT, P=0.16. Median number of collections was 3 in both. More patients in the LT (67%) received Melphalan 200 mg/m2 conditioning compared to ET (59%) p=0.03. Neutrophil engraftment occurred at day + 11 ET and +12 (LT) p<0.0001. ET patients achieved platelet engraftment on day + 13 compared to + 15 (LT) p=0.002. Complete response rates were similar 30% (ET) and 34% (LT). Duration of response after PBSCT was not different 12.6 months (ET) and 11.6 months (LT). Median overall survival from diagnosis was 70.5 months (ET) and 74.5 months (LT) p=0.5. Similarly there was no difference in overall survival post PBSCT 33.5 month (ET) and 32.2 months (LT). Conclusion: Stem cell collection and storage early in the disease course of multiple myeloma results in early engraftment compared to stem cell collection at the time of transplant in patients who opt for a delayed transplant. More studies looking at cost analysis will however be need to determine the cost effectiveness of early versus late stem cell collection. Disclosures: Dispenzieri: Celgene: Honoraria, Research Funding; Binding Site: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Millennium: Research Funding; Merck: Consultancy, Research Funding; Novartis: Research Funding; Genzyme: Consultancy, Research Funding; Cephalon: Research Funding. Gertz:Celgene: Honoraria; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees.

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