Lenalidomide Consolidation Followed by Maintenance After Autologous Transplantation for Multiple Myeloma Decreases Thymic Output and Terminally Differentiated CD4 and CD8 T Cells but Increases Treg

Abstract Abstract 4046 Treatment with lenalidomide, an immunomodulatory drug, increases the time to progression in relapsed/refractory multiple myeloma. However, due to its pleiotropic effect, it is not known whether the efficacy of this drug is due only to direct tumor toxicity or also to immunomodulatory effects. We assessed in vivo the changes in T-cell reconstitution induced by lenalidomide consolidation and maintenance treatment following autologous peripheral blood stem cell transplantation (ASCT) in a cohort of multiple myeloma patients. Twenty-nine newly diagnosed myeloma patients were treated with the induction combination bortezomib plus dex followed by high dose melphalan (140–200 mg/m2) and ASCT. A first group of 11 patients were treated with lenalidomide consolidation initiated 3 to 6 months post transplantation: 25 mg/day, days 1–21 of a 28 day cycle for 2 months, followed by maintenance (10 mg/day) until disease progression. This group was compared with the 18 patients who did not receive any treatment after ASCT. Blood samples were collected at diagnosis, before the transplant and 1, 3, 6, 9, 12 and 18 months after ASCT. Thymic function was assessed by real-time PCR quantification of T cell receptor excision circles (sjTREC) and percentages and absolute counts of T lymphocyte subpopulations were determined by multicolor flow cytometry. Statistics were performed using the Log-Rank or Mann-Whitney test. The two cohorts had similar baseline characteristics and all 29 patients were in remission after ASCT. With a median follow-up of 4 years, progression-free survival (PFS) was superior with lenalidomide treatment (69% vs 36%, p=0.05) while overall survival (OS) was similar (82% vs 75%, p=0.5). Lenalidomide treatment induced a progressive decrease in sjTREC (median at 18 months, 0.25/μL vs 1.61/μL, p<0.05) and a decrease in the percentages and absolute counts of CD4+ and CD8+ CD45RA+CCR7- effector terminal T cell subpopulations (median at 18 months, 3.2/μL vs 17.6/μL, p<0.05 for CD4+CD45RA+CCR7- and 109/μL vs 345/μL, p<0.05 for CD8+CD45RA+CCR7-). Conversely, lenalidomide treated patients displayed an increase in CD4+CD25+CD127-/low Treg populations, in both percentage and absolute count (median 13% vs 8 %, p<0.05 and 48.9/μL vs 29.3/μL, p<0.05, respectively). No correlation was found with documented infections, relapse or survival. We confirm an increase in PFS with lenalidomide consolidation/maintenance following ASCT. However, our data also suggest that in myeloma patients, the effect of lenalidomide on the myeloma tumor may not be T cell mediated and this treatment may have a negative impact on the T cell immune surveillance. Disclosures: No relevant conflicts of interest to declare.

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Bortezomib Administered Subcutaneously Is Well Tolerated in Bortezomib-Based Combination Regimens Used in Patients with Multiple Myeloma and AL Amyloidosis

Blood ◽

10.1182/blood.v118.21.5124.5124 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5124-5124

Author(s):

Wolfgang Lamm ◽

Beatrice Schauer ◽

Sandra Eder ◽

Christoph Zielinski ◽

Johannes Drach

Keyword(s):

Multiple Myeloma ◽

Side Effects ◽

Conflicts Of Interest ◽

Negative Impact ◽

Autologous Transplantation ◽

Al Amyloidosis ◽

Recent Trial ◽

Skin Reactions ◽

Local Skin ◽

Combination Regimens

Abstract Abstract 5124 Introduction: Novel agents like the proteasome inhibitor bortezomib (Btz) and immunomodulatory agents show activity in multiple myeloma (MM) as well as in primary AL amyloidosis (AL). Btz has emerged as a standard of care in the treatment of patients with MM and AL. The approved dose and schedule of Btz is 1.3mg/m2 administered on days 1, 4, 8, and 11 as an intravenous (i.v.) bolus injection. However, among several side effects, peripheral neuropathy (PN) has a particular negative impact on the quality of life of patients treated with Btz. A recent trial provided evidence for a similar efficacy of Btz administered subcutaneously (s.c.) compared to i.v. administration, but side effects including PN were significantly less frequent with s.c. application of Btz. Here we report our experience regarding efficacy and tolerability of treatment with Btz administered s.c. in patients with MM and AL. Patients and Methods: 19 consecutive patients with MM (n = 17) or histologically proven AL (n = 2) were included in this analysis. For s.c. administration, Btz was prepared at a concentration of 2.5 mg/mL (as opposed to an i.v. concentration of 1.0 mg/mL). All patients received Btz at a dose of 1.3 mg/m2 on days 1, 4, 8, and 11. Btz was used in combination regimens with dexamethasone (n = 9), with thalidomide/dexamethasone prior to autologous transplantation (VDT; n = 6), or with melphalan/prednisolone in elderly patients (VMP; n = 4). Results: Patients (male n=7; female n=12) were at a median age of 64 years (range 38–77), and 11 patients (58%) received the Btz-based regimen with Btz s.c. as their first line treatment. At the time of analysis, a median of 3 cycles bortezomib s.c. (range, 1–5) have been administered. Hematological toxicities were only at Grades 1+2 and included anemia (78%) and thrombocytopenia (33%). Only one patient developed a grade 3 PN, and this patient already had pre-existing PN due to prior i.v. administration of Btz. Other non-hematologic side effects were at grades 1+2 including fatigue (11%) and local skin reactions at the site of s.c. injection, which were self-limited. No notable gastrointestinal toxicity was observed, and therefore we stopped the routine use of i.v. hydration and antiemetics, which were previously administered as concomitant therapy with i.v. Btz. Of 14 MM patients so far evaluable for response, 12 (86%) had a PR or better including 5 patients (36%) achieving a CR. Both patients with AL achieved a very good partial remission (VGPR). More data on efficacy with longer follow-up will be presented at the meeting. Conclusion: Our observations confirm the improved toxicity profile of the s.c. administration of Btz in various standard Btz-based combination regimens. In addition, due to the ease of s.c. administration of Btz, patient management has been markedly facilitated at our centre. Disclosures: No relevant conflicts of interest to declare.

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Prevalence of Oligoclonal Bands in Multiple Myeloma Patients Who Achieved Better Results Than Very Good Partial Response after Treatment with Standard or High Doses Chemotherapy-Final Analysis

Blood ◽

10.1182/blood.v126.23.4210.4210 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4210-4210

Author(s):

Luiza soares Vieira ◽

Edvan de queiroz Crusoe ◽

Manuella de S. Sampaio Almeida ◽

Lais Sousa ◽

ana Lucia Perez ◽

...

Keyword(s):

Multiple Myeloma ◽

Partial Response ◽

Conflicts Of Interest ◽

Progression Free Survival ◽

Final Analysis ◽

Complete Response ◽

High Dose Chemotherapy ◽

Oligoclonal Bands ◽

High Dose ◽

Good Partial Response

Abstract Introduction - Oligoclonal bands (OB) are monoclonal proteins distinct from those originally identified in the multiple myeloma (MM) diagnosis. Some authors consider that appearance of these bands confers a better prognosis and may be linked to immune reconstitution. There is no data of the exact prevalence of OB emergence in patients with very good partial response (VGPR) or better after different treatment schedules. Objectives - To determine the prevalence of OB in MM patients treated with or without high-dose chemotherapy that obtained at least VGPR and its prognostic value. Methods- This is a retrospective and prospective cohort study. Data were collected from records of patients that achieved at least VGPR to identify the OB emergence. Subsequently, new sample collections from the positive patients were made in order to monitor the progress and duration of the maintenance of these bands. Results-Median follow-up was 42m and 101 patients were included. Median age was 58y (29-87) and 55% were male. IgG was the most frequent component (60%). Durie-Salmon IIIA/B was identified in 92% of the population; ISS was 33% in stage I, 30% in stage II, and 31% in stage III. The prevalence of OB identified by SPE and IF was 50.5% (51 cases), with a higher prevalence in those who underwent transplantation and those who achieved complete response (p=0.00139 and p=0.0368, respectively). Progression free survival (PFS) was longer in the OB group (45.4m x 34.7m p = 0.0075). Conclusion - The OB prevalence in this population was 50.5% and oligoclonality resulted in a longer PFS. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Stem Cell Mobilization after Various Induction Regimens in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v126.23.5433.5433 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5433-5433

Author(s):

Jakub Radocha ◽

Vladimir Maisnar ◽

Miriam Lanska ◽

Jiri Hanousek ◽

Katerina Machalkova ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Conflicts Of Interest ◽

Rapid Development ◽

Autologous Transplantation ◽

Stem Cell Mobilization ◽

High Dose ◽

Cell Transplant ◽

Cell Mobilization ◽

Stem Cell Collection

Abstract Stem cell mobilization after various induction regimens in patients with multiple myeloma Introduction: Rapid development of novel therapies for multiple myeloma has led to a significant improvement in response to the treatment. Stem cell mobilization before autologous stem cell transplantation is a source of considerable costs of transplant procedure. Whether modern induction regimens affect outcome of stem cell mobilization has not been extensively studied. Aim: The goal of this study was to compare efficacy of stem cell mobilization after different induction regimens in patients with multiple myeloma. The primary goal was to compare CTD (cyclophosphamide, thalidomide, dexamethasone), CVD (cyclophosphamide, bortezomib, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) and regimens in terms of succesful stem cell collection. Methods: All patients with multiple myeloma who have been planned for stem cell collection and were treated with one of the above mentioned regimens were included in this retrospective analysis. The demographic data, amount of stem cells collected, number of days needed to reach the target collection were recorded. All patients received high dose cyclophosphamide 2,5 g/m2 prior to stem cell collection and were primed with G-CSF twice daily from day 5. The collection was started at day 10. Collection goal was 8x106/kg CD34+ cells. Results: 15 patients received CTD, 25 patients CVD and 16 patients VTD regimen before stem cell collection. Groups were comparable according to age, gender and myeloma stages. Mean collected cells at the end of collection were 9.2 (SD 2.8) for CTD, 12.3 (SD 5.6) for CVD and 10.1 (SD 2.1) for VTD (p=0.066). Mean daily harvest was 3.4, 8.0 and 7.6 x106/kg respectively (p=0.01). Mean days needed to reach desired harvest were 3, 2.25 and 1.6 days (p=0.001). No collection failure was observed. Conclusion: The best collection results were seen in patients after induction with CVD or VTD regimen. VTD regimen also required the least days for collection and seems to be most beneficial for cost of collection. CTD regimen shows the least efficacy in stem cell collection before autologous transplantation. All patients managed to harvest for at least one stem cell transplant. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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Relapsed Multiple Myeloma: Who Benefits From Salvage Autografts?

Blood ◽

10.1182/blood.v118.21.3059.3059 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3059-3059 ◽

Cited By ~ 1

Author(s):

Annie W.S. Chow ◽

Cindy H.S. Lee ◽

Devendra K Hiwase ◽

Luen Bik To ◽

Noemi Horvath

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Conflicts Of Interest ◽

Selection Criterion ◽

South Australia ◽

Progression Free Survival ◽

Novel Agents ◽

High Dose ◽

Cell Transplant ◽

Free Interval

Abstract Abstract 3059 Aim Despite novel agents, multiple myeloma (MM) remains incurable. The majority of patients with MM will relapse at some stage after induction therapy and high dose chemotherapy with autologous stem cell transplant (ASCT). Published studies have recommended salvage ASCT as an effective option in patients with relapsed MM. However, the patient cohort who will derive maximum benefit from salvage ASCT is still undefined and is likely to evolve with increasing therapeutic options. We aimed to evaluate the role of salvage ASCT in relapsed MM patients. Methods We performed a retrospective analysis of patients who underwent salvage ASCT for relapsed MM in South Australia between 1992 and 2011. Results During this period, autologous stem cell transplants were performed for 457 patients with newly diagnosed MM. Thirty-nine patients subsequently underwent salvage ASCT for relapsed MM. The median age of patients at salvage ASCT was 59 (34–73) years, and 85% were ISS I and II at diagnosis. The majority of patients (90%, n=35) had a progression free interval (PFI) of at least 12 months after initial ASCT, consistent with recommendations by current literature. Salvage ASCT was performed for four patients with PFI shorter than 12 months, due either to suboptimal response to novel agents (thalidomide, lenalidomide, bortezomib), or the lack of novel agent availability in the earlier years. The median progression-free survival (PFS) and median overall survival (OS) following salvage ASCT were 22 months (95% CI: 11–32) and 52 months (95% CI: 30–74) respectively. Non-relapsed mortality at 2 years was 7%. Following salvage ASCT, the median PFS (28 vs. 12 months, p = 0.006) and OS (83 vs. 26 months, p = 0.02) were significantly longer in patients whose progression free interval after the initial ASCT was > 24 months (Figures 1 and 2). Use of novel agents in salvage induction and maintenance therapy post salvage ASCT did not appear to influence outcome. Conclusion Our results suggest that there remains a role for salvage ASCT, even in the era of novel therapies. Salvage ASCT may result in durable responses, particularly in patients with longer progression free interval (> 24 months) following initial ASCT. This interval could be included as a selection criterion for patients with relapsed myeloma who remain transplant eligible. Disclosures: No relevant conflicts of interest to declare.

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First and Second High Dose Treatment Supported by Autologous Hematopoetic Cell Transplantation Rescue in Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.4528.4528 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4528-4528

Author(s):

Sinem Civriz Bozdag ◽

Pervin Topcuoglu ◽

Meral Beksac ◽

Osman Ilhan ◽

Muhit Ozcan ◽

...

Keyword(s):

Multiple Myeloma ◽

Cell Transplantation ◽

Median Time ◽

Conflicts Of Interest ◽

Early Period ◽

Progression Free Survival ◽

Response Rates ◽

High Dose ◽

Hematopoietic Stem ◽

Free Survival

Abstract Abstract 4528 Purpose: We aimed to evaluate the outcome of multiple myeloma patients underwent double autologus hematopoietic cell transplantation in our center. Patient&Method: We retrospectively analyzed 31 multiple myeloma patients (22F;9M) receiving two times high dose therapy supported by auto-HCT in Adult BMT Unit of Ankara University between 2005–2010. Median age was 52 years (34–66ys) prior to first auto-HCT. We evaluated the response rates of progression free survival (PFS) of both transplantation, respectively and also overall survival (OS) from the diagnosis. Results: The median time from diagnosis to the first transplantation was 11 months (5–68ms). The response rates were 87% before the first auto-HSCT [2 Complete response (CR),4 near-CR, 7 very good partial remission (VGPR), 14 PR) but four patients (11%) had refractory disease. The response of first auto-HCT was complete remission or partial response in 50% of the pts and 36% for stable disease. Only 4 pts was progressed at early period of 1st auto-HCT. The median time from the 1st to 2nd auto-HSCT was 16 months (3–64 ms). Seventy-seven percent patients sue to progressive disease responded completely or partially to one or two step treatment regimens before the second auto-HSCT. When evaluated the responses after the second auto-HCT, 14 (46%) patients were in CR or near-CR, 12 (38%) for stabile disease and 5 for refractory. PFS was estimated similar after both first and second auto-HCT (median 9 months vs 10 months, p=0.3) (Graphic 1). Five- year OS from the diagnosis was 75±10%. Conclusion: PFS of the myeloma pts was estimated similar median time after 1st&2nd auto-HSCT. Collection of adequate hematopoietic stem cells enough for more than one auto-HCT in myeloma patients can be appropriate. Although the majority of responses after the first AHSCT were partial responses, complete or near complete responses were dominant after the second AHSCT.Improvement in responses and the similarity of progression free survival can be explained by the contribution of the new antimyelom treatment options Disclosures: No relevant conflicts of interest to declare.

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Evidence for naive T-cell repopulation despite thymus irradiation after autologous transplantation in adults with multiple myeloma: role of ex vivo CD34+ selection and age

Blood ◽

10.1182/blood-2002-06-1929 ◽

2003 ◽

Vol 101 (5) ◽

pp. 1891-1897 ◽

Cited By ~ 21

Author(s):

Marion Malphettes ◽

Guislaine Carcelain ◽

Pierre Saint-Mezard ◽

Véronique Leblond ◽

Hester Korthals Altes ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cells ◽

T Cell ◽

Cd4 T Cells ◽

Autologous Transplantation ◽

High Dose ◽

T Cell Reconstitution ◽

Unselected Group ◽

Cell Repopulation

Immunodeficiency following autologous CD34+-purified peripheral blood stem cell (PBSC) transplantation could be related to T-cell depletion of the graft or impaired T-cell reconstitution due to thymus irradiation. Aiming to assess the role of irradiated thymus in T-cell repopulation, we studied 32 adults with multiple myeloma, randomly assigned to receive high-dose therapy including total body irradiation (TBI) followed by autologous transplantation with either unselected or CD34+-selected PBSCs. The median number of reinfused CD3+ cells was lower in the selected group (0.03 versus 14 × 106/kg; P = .002). Lymphocyte subset counts were evaluated from month 3 to 24 after grafting. Naive CD4+ T cells were characterized both by phenotype and by quantification of T-cell receptor rearrangement excision circles (TRECs). The reconstitution of CD3+ and CD4+ T cells was significantly delayed in the CD34+-selected group, but eventually led to counts similar to those found in the unselected group after month 12. Mechanism of reconstitution differed, however, between both groups. Indeed, a marked increase in the naive CD62L+CD45RA+CD4+subset was observed in the selected group, but not in the unselected group in which half of the CD45RA+CD4+ T cells appear to be CD62L−. Age was identified as an independent adverse factor for CD4+ and CD62L+CD45RA+CD4+ T-cell reconstitution. Our results provide evidence that infusing PBSCs depleted of T cells after TBI in adults delays T-cell reconstitution but accelerates thymic regeneration.

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Lenalidomide with Low-Dose Dexamethasone (Rd) Continuously Versus Rd Induction, Tandem MEL140 with Autologous Transplantation and Lenalidomide Maintenance: Planned Interim Analysis of a Prospective Randomized Trial in Patients 60-75 Years of Age with Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.3969.3969 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3969-3969 ◽

Cited By ~ 1

Author(s):

Christian Straka ◽

Kerstin Schaefer-Eckart ◽

Florian Bassermann ◽

Hansen Timon ◽

Bernd Hertenstein ◽

...

Keyword(s):

Multiple Myeloma ◽

Stem Cell ◽

Low Dose ◽

Autologous Transplantation ◽

Progression Free Survival ◽

Stage I ◽

High Dose ◽

Free Survival ◽

Cell Mobilization ◽

High Dose Melphalan

Abstract Background: Lenalidomide with low-dose dexamethasone (Rd) is an emerging treatment option for newly diagnosed multiple myeloma patients with higher age. However, many older patients also remain candidates for autologous transplantation especially with age-adjustment of high-dose melphalan. Potentially, high-dose therapy could add to the benefit of Rd, alternatively the effect of high-dose therapy could be more or less redundant in this setting. The DSMM XIII trial is a multicenter, open-label, phase III trial comparing the safety and efficacy of continuous Rd versus Rd induction followed by age-adjusted tandem high-dose melphalan with autologous transplantation and lenalidomide maintenance. Methods: Patients with newly diagnosed multiple myeloma with symptomatic and measurable disease of age 60-75 years were randomly assigned to either (A1) lenalidomide (25 mg po d1-21/28d) with low-dose dexamethasone (Rd) (40 mg po d1, d8, d15, d22/d28) for 3 cycles followed by stem cell mobilization and continued Rd until progression or (A2) 3 cycles of Rd, followed by stem cell mobilization, tandem high-dose melphalan 140 mg2 (MEL140) with autologous blood stem cell transplantation and lenalidomide maintenance 10 mg daily until progression. At randomization, patients were stratified according to age (≤70 years vs >70 years) and ISS stage (I, II vs III). Antithrombotic prophylaxis with low molecular weight (LMW) heparin or aspirin was recommended. The primary endpoint was progression-free survival (PFS), and secondary endpoints included safety, responses, overall survival and others. We report the results of the planned first interim analysis after occurrence of one third of events as pre-specified. Results: Since March 2010, 253 patients have been randomized and data of 251 patients were available for analysis. The median age was 68 years (range 59-75), 30% were older than 70 years, 34% had ISS stage I, 37% ISS stage II, and 29% ISS stage III. The median PFS for the whole study population (A1 and A2) was 37.3 months. The comparison of PFS by randomization arm did not meet the formal criteria for early termination of the trial. The overall response rate after 3 cycles of Rd (A1 and A2) was 75%, with 2% demonstrating complete response (CR), 21% very good partial response (VGPR) and 52% partial response (PR). A further 20% of patients had stable disease and 6% of patients progressive disease. The 3-year-survival rate is 75% (95% confidence interval, 68-84) for all patients and with respect to ISS stage amounted to 90% (CI: 81-99, ISS stage I), 78% (CI: 66-91, ISS stage II) and 51% (CI: 35-74, ISS stage III). For the two age groups, the 3-year-survival was 73% (CI: 64-84) in patients with age ≤70 years and 80% (CI: 68-94) in patients with age >70 years. So far, 8 (3%) second primary malignancies (SPM) were observed, 4 skin tumors and 4 other solid tumors, but no hematological SPM was documented. Conclusion: In our trial, lenalidomide with low-dose dexamethasone (Rd) was found to be associated with a favorable median progression-free survival at 3 years. The survival in patients >70 years was not inferior compared to younger patients. The potential advantages and disadvantages of combining lenalidomide with high-dose melphalan and autologous transplantation in comparison to continous Rd are addressed by this ongoing trial and further data will be presented at the meeting. Disclosures Straka: Celgene: Consultancy, Honoraria, Research Funding. Off Label Use: Lenalidomide for first-line treatment.

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Autologous Haematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma Complicated By Dialysis-Dependent Renal Failure

Blood ◽

10.1182/blood-2018-99-115880 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5765-5765

Author(s):

Maiia V. Firsova ◽

Larisa P. Mendeleeva ◽

Irina G. Rekhtina ◽

Maxim V. Solovev ◽

Olga S. Pokrovskaya ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Failure ◽

Conflicts Of Interest ◽

Survival Rates ◽

Progression Free Survival ◽

Treatment Method ◽

High Rate ◽

Haematopoietic Stem Cell ◽

Post Transplantation ◽

Renal Response

Abstract Introduction. Multiple myeloma (MM) in its early onset is complicated by myeloma nephropathy in 20-30% of patients, 10% of whom require haemodialysis. Early studies have shown that renal dysfunction has no adverse effect on melphalan pharmacokinetics. Auto-HSCT in some patients allows to restore renal function and to stop hemodialysis. Aim of the study. To assess the safety and efficacy of auto- HSCT in MM patients with dialysis-dependent renal failure. Materials and methods. During a period from May 2010 to December 2016 thirteen (3 males, 10 females) MM patients with dialysis-dependent renal failure aged 48 to 65 years (median 58) underwent auto-HSCT. The diagnosis was made according to IMWG criteria. In the onset of the disease, the median creatinine level was 1091 μmol /L, and GFR (CKD-EPI) ranged 3 to 10 ml / min / 1.73 m2 (median 3). Induction therapy included bortezomib-containing regimens in all patients, bendamustine was used in 5 (38.5%) patients, immunomodulatory drugs were used in 2 (15%) patients. HSC mobilization was performed according to the scheme: G-CSF 10 μg/kg. The median number of harvested CD34+ cells was 3.46x106/kg. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100-200 mg/m2), 12 patients underwent a single and one patient underwent a tandem auto-HSCT. On Day 100 after auto-HSCT, an antitumor response and renal response were assessed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10. Results. Before auto-HSCT CR was documented in 8 (61%) patients, VGPR was documented in 4 (31%) patients, PR was documented in 1 (8%) patient, with no renal response registered, GFR: 4-10 ml/min/1.73 m2 (median 5). The period of agranulocytosis after auto-HSCT was accompanied by infectious complications, cardiac and neurological dysfunctions (Table 1). The resulting complications were stopped; the mortality associated with transplantation (TRM) was 0%. At +100 days after auto-HSCT, the PR was confirmed in 9 (70%) patients and VGPR was confirmed in 4 (30%) patients. GFR: 5 - 17 ml/min/1.73 m2 (median 7). The minimal renal response was registered in 2 patients (15%), hemodialysis was stopped. After a median follow-up of 52 months 5-year progression-free survival (PFS) was 71%, and OS was 92%. Conclusion. Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, nevertheless, characterized by a high rate of early post-transplantation complications. Dialysis-dependent renal failure is not a contraindication for the use of high dosed melphalan followed by auto-HSCT. The probability of hemodialysis discontinuation after auto-HSCT was 15%. Survival rates are comparable to those in patients without renal impairment. Disclosures No relevant conflicts of interest to declare.

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Bortezomib-Containing Regimens for Multiple Myeloma Maintenance Therapy: a Meta-Analysis

Blood ◽

10.1182/blood.v124.21.3473.3473 ◽

2014 ◽

Vol 124 (21) ◽

pp. 3473-3473

Author(s):

Yucai Wang ◽

Wenwen Zhang ◽

Fang Yang ◽

Xiaoxiang Guan ◽

Neil Kothari ◽

...

Keyword(s):

Multiple Myeloma ◽

Adverse Events ◽

Maintenance Therapy ◽

Conflicts Of Interest ◽

Meta Analysis ◽

Progression Free Survival ◽

High Dose ◽

Vascular Events ◽

Cardiac Disorders ◽

Grade 3

Abstract Objective: To evaluate the efﬁcacy and safety of bortezomib-containing regimens in maintenance therapy of multiple myeloma through meta-analysis of randomized controlled trials (RCTs). Patients and methods: PubMed, Web of Science and ASH databases were searched for RCTs that investigated the treatment outcomes (progression-free survival [PFS] and overall survival [OS]) of maintenance therapy with bortezomib-containing regimens in patients with multiple myeloma. Study endpoints included PFS, OS, and grade 3 or 4 adverse events. Pooled hazard ratios (HRs) for survival outcomes and risk ratios (RRs) for dichotomous data with 95% confidence interval (CI) were calculated using Comprehensive MetaAnalysis (v2). Results: Three RCTs comprising 1396 patients were included in this meta-analysis. Compared with maintenance therapy without bortezomib and/or no maintenance therapy, bortezomib-based maintenance therapy regimens significantly prolonged PFS (HR = 0.66, 95% CI = 0.58 - 0.76, P < 0.001) and OS (HR = 0.74, 95% CI = 0.62 - 0.88, P = 0.001) in multiple myeloma patients. In patients who received high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), bortezomib-based maintenance therapy increased both PFS (HR = 0.73, 95% CI = 0.61 - 0.86, P < 0.001) and OS (HR = 0.76, 95% CI = 0.61 - 0.95, P = 0.016). For transplant ineligible patients, maintenance therapy with bortezomib-containing regimen also increased PFS (HR = 0.58, 95% CI = 0.47 - 0.71, P < 0.001) and OS (HR = 0.70, 95% CI = 0.52 - 0.92, P = 0.012). However, bortezomib-based maintenance therapy increased the risks of grade 3 or 4 adverse events including thrombocytopenia (RR = 1.37, 95% CI = 1.01 - 1.87, P = 0.046), infections (RR = 1.29, 95% CI = 1.02 - 1.64, P = 0.035), cardiac disorders (RR = 2.01, 95% CI = 1.17 - 3.47, P = 0.012), and vascular events (RR = 2.02, 95% CI = 1.15 - 1.45, P= 0.015). Conclusions: Bortezomib-based maintenance therapy results in signiﬁcant improvement in PFS and OS in multiple myeloma patients, but may increase the risk of developing some grade 3 or 4 adverse events, such as thrombocytopenia, infections, cardiac disorders, and vascular events. Further studies are needed to corroborate the above findings given the limited data on proteasome inhibitor based maintenance therapy for multiple myeloma. Disclosures No relevant conflicts of interest to declare.

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Effectiveness of Lenalidomide and Dexamethasone for the Treatment of Extramedullary Plasmacytoma in Patients with Multiple Myeloma: Report of Two Cases

Blood ◽

10.1182/blood.v124.21.5760.5760 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5760-5760

Author(s):

Katarína Masárová ◽

Zdenka Stefanikova ◽

Martin Mistrik ◽

Angelika Batorova

Keyword(s):

Multiple Myeloma ◽

Complete Remission ◽

Conflicts Of Interest ◽

Bone Marrow Involvement ◽

Progression Free Survival ◽

Primary Diagnosis ◽

Extramedullary Plasmacytoma ◽

High Dose ◽

Solitary Plasmacytoma ◽

High Dose Dexamethasone

Abstract Extramedullary plasmacytoma (EMP) can occur at the time of primary diagnosis of multiple myeloma (MM), during the disease, or as solitary plasmacytoma without bone marrow involvement. The presence of EMP at any time in the course of disease is associated with significantly shorter overall survival and progression-free survival. We report a series of two patients with EMP who were successfully treated with lenalidomide and dexamethasone. The first patient was diagnosed in 2006 with EMP in the spine without presence of MM at the time of diagnosis. Reconstruction surgery followed by high dose dexamethasone treatment led to stabilization of patient’s condition. Patient received zoledronic acid for prevention of skeletal fractures. In 2011 the patient was diagnosed with MM and two new EMP lesions in the spine were discovered. The patient received bortezomib and achieved a partial remission. In 2012 a significant growth of EMP in retroperitoneum was observed. Tumor was surgically removed, plasmacytoma was confirmed histologically. Patient was treated with lenalidomide and dexamethasone with subsequent autologous peripheral blood stem cell transplantation (APBSCT) and achieved complete remission. Patient Two had advanced stage of MM at the time of diagnosis, without presence of EMP. She was treated with induction therapy followed by APBSCT. EMP in the area of clivus, diagnosed three years after initial diagnosis of MM was successfully managed with conventional chemotherapy and radiotherapy. In 2010 another EMP in the left sphenoid sinus progressed during relapse of MM. Treatment with lenalidomide and dexametazone led to remission of MM and disparition of EMP. Both patients are in complete remission at the time of submitting this abstract. Our clinical experience strongly suggests that lenalidomide with dexamethasone is an effective agent for treating EMP in patients with MM. The treatment was well tolerated with manageable side effects. Disclosures No relevant conflicts of interest to declare.

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