The Dream of a Cure in Multiple Myeloma: A 15-Year Single Center Retrospective Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5503-5503
Author(s):  
Stefano Pulini ◽  
Annalisa Natale ◽  
Anna Maria Morelli ◽  
Antonio Spadano ◽  
Stefano Angelini ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Progressive Disease ◽  
Diagnostic Tools ◽  
Cell Transplant ◽  
The Past ◽  
Line Therapy

Abstract Multiple Myeloma (MM) is still considered an incurable disease despite a substantial global outcome improvement observed during the past decade. Despite better understanding of biological pathways, availability of sophisticated diagnostic tools and increasing number of therapeutic options almost all patients experience disease relapse. The aim of our retrospective study was to analyze global outcome in newly diagnosed MM patients eligible for high dose chemotherapy and autologous stem cell transplant (ASCT) treated in our Institution in the last 15 years. We evaluated 177 MM patients transplanted in our Institution from November 1999 to February 2015. Median age at start therapy was 58 years (range 36-71) and median follow up time (from start therapy to last follow up) was 52 months (range 7-185). Patients received different induction therapies before transplant reflecting the availability of new drugs and consequently more therapeutic choices. 65 patients received conventional chemotherapy-based induction (VAD 27, 15%, Total Therapy 2-like 37, 22%, EDAP 1 patient); 15 patients thalidomide-based (TD, 8%); 88 patients bortezomib-based (VTD 74, 43%; VCD 8, 5%; PAD 3, 1%; VD 3, 1%) and 9 patients lenalidomide-based (RD, 5%). After induction regimen 23 patients (13%) received additional therapy before transplant: 14 for Progressive Disease (PD), 9 were considered in suboptimal/unsatisfactory response (5 in Partial Response, PR and 4 in Stable Disease, SD). 71 patients received a single ASCT, 106 patients double ASCT; 11 tandem autologous and allogeneic SCT. All patients had a PR/VGPR/CR after ASCT. Treatment related mortality was 1% (3 patients: 2 of them after Allogenic ASCT, 1 for acute Graft versus Host Disease, 1 for Veno Occlusive Disease). After first line therapy 7 patients died: 3 for progressive disease, 4 for other causes (2 myocardial infarction, 1 intestinal ischemia and 1 breast cancer). 90 patients (51%) experienced MM relapse (median time from ASCT 24 months) and were treated according to different chemotherapy schedules. At last follow-up 115 patients were alive (65%), 61 of them in Complete Response, 31 in Very Good Partial Response, 8 in Partial Response, 4 in SD, 11 in PD. Median global overall survival (OS) was 109 months, median global Progression Free Survival1 (PFS1) 51 months and median global PFS2 (time from start therapy to second disease progression or death from any cause) 80 months. According to different induction therapy (chemotherapy vs bortezomib vs thalidomide vs lenalidomide-based) median OS was 117 months vs not reached (more than 96) vs 68 vs not reached (more than 60); median PFS1 was 47 months vs 60 vs 35 vs not reached (more than 60); median PFS2 was 76 months vs 92 vs 57 vs not reached (more than 60), respectively. As reported in literature the improvement of biological, diagnostic and clinical knowledge and the availability of new therapeutic tools translates in improved outcome in MM patients treated in our Center. The introduction of the proteasome inhibitor bortezomib in the induction therapy gave the best results in terms of OS, control of the disease (PFS) and response to second line therapy after relapse (PFS2). Considering the remarkable progress done in the past decade the dream of a cure is a challenge for the future. Disclosures No relevant conflicts of interest to declare.

Treatment Patterns & Survival In Multiple Myeloma Patients Sequentially Exposed To Thalidomide, Bortezomib & Lenalidomide In a UK Single Centre

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5380-5380 ◽  
Author(s):  
Julie L Tarant ◽  
John Ashcroft ◽  
Sylvia Feyler ◽  
Roger G Owen ◽  
Christopher Parrish ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Progressive Disease ◽  
Response To Therapy ◽  
High Dose ◽  
Second Line ◽  
Single Centre ◽  
Line Therapy ◽  
Wide Range ◽  
Duration Of Response

Abstract Background In recent years, the introduction of the immunomodulatory drugs (IMiDs) thalidomide & lenalidomide & the proteasome inhibitor (PI) bortezomib has substantially improved the therapeutic options & prolonged survival of patients (pts) with multiple myeloma (MM). Current treatment strategies involve sequential exposure to these agents, though the most effective sequencing of exposure has yet to be determined. MM is still, for the majority of pts, a relapsing & incurable disease with poor survival outcomes & alternative treatment approaches in relapsing disease after exposure to currently available novel agents is an on-going unmet need. We report the results of extended follow-up in this patient cohort. Objectives We examined outcomes in pts with progressive disease following sequential exposure to thalidomide, bortezomib & then lenalidomide, to assess responses to these & subsequent therapies in a “real-life” single centre setting. Methods Pts were eligible for this retrospective study if they had received sequentially thalidomide-, bortezomib- then lenalidomide-based combination therapy (LenCom) for MM as per The National Institute for Health & Care Excellence (NICE) guidance. Case records were examined for diagnostic details, depth & duration of response to PI treatment & regimens employed. T0 was defined as the time point at which LenCom was discontinued, whether for progressive disease (PD) or intolerance (I). Response to therapy subsequent to T0& Progression Free Survival/Overall Survival (PFS/OS) were assessed & factors predicting outcome analysed (e.g. ISS stage at diagnosis, age, previous therapies received, previous depth & length of response to treatment). Results Between Jan’07-Sept’12, 55 pts (27 Male & 28 Female) were enrolled. Median age at diagnosis was 59 yrs (range 33-89);ISS scores were: 20% stage I, 28% stage II & 28% stage III (23% unclassified). The median number of lines of therapy prior to LenCom was 3 (range 2-6). First line therapy was thalidomide-based in 64%; 36% underwent ASCT & 4 pts underwent tandem ASCT/RIC AlloSCT. Second line therapy was bortezomib-based in 42% &  53% pts received lenalidomide as > 4th line. Median time from diagnosis to commencing LenCom was 52.5mns (range 4-146). 43 pts (77%) had reached T0 (PD n=29, I n=14). At a median of 66 mns follow up (range 12-162 mns), a median of 9 cycles (range 1-32) of LenCom were administered to all pts & 7 cycles (range 1 -32) to those who had discontinued LenCom. Dexamethasone was discontinued after median 12 cycles in pts reaching T0, being stopped in 28% (median 6 cycles before T0). Median PFS from commencement of LenCom was 16.2 mns. At 4 mns median follow-up post T0, a total of 26 pts have received therapy after T0, of whom 3 received lenalidomide-based treatment (11.5%) & 3 received bortezomib-based treatments (11.5%). Thalidomide based treatment was received by 13 pts (combined with Bendamustine in 3 & bortezomib in 2). Post-T0 pts also received clinical trial therapies (3 pts on SRT501 trial, 1 pt on pomalidamide companion study & 1 pt on KW2478 – a heat shock protein 90 inhibitor), thalidomide-based treatment (10 pts, 2 with bortezomib), & high dose dexamethasone. 13 pts (50%) demonstrated PD as maximum response to first post-T0 therapy. Duration of response was generally very limited (median 0 mns, range 0-6 mns). Second line post T0 treatments, including pomalidomide, were received by 12 pts with only 2 pts pts achieving a PR or better to Thalidomide & bortezomib based regimens. Third line post T0 treatments were given to 2 pts with 1 pt achieving a further brief PR to DT-PACE. With a median follow-up of 6.4mns (1-37), 31 pts have died (PD n=18, infection n=6, other n=7). Median OS from diagnosis & commencement of LenCom were 100 mns & 18.4 mns, respectively. Median OS from T0 was 3.9mns (range 0-33 mns), influenced by the b2-microglobulin at T0 (<vs.³ 3.0 mg/L: 9 vs. 4.8 mns, p=0.027). The depth of response to LenCom correlated with PFS (P<0.001) but not post-T0OS (p=0.68). Conclusion Pts with MM who have relapsed after sequential exposure to thalidomide, bortezomib & lenalidomide have very limited treatment options. At present, a wide range of treatments are used, including re-challenging with lenalidomide, bortezomib & trial based treatments. However, few pts achieve a meaningful response to therapy & survival is consequently extremely poor. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Impact of RVD or VCD Induction on Response 3 Months after First Line Autologous Transplant in Multiple Myeloma. a Single-Center Retrospective Analysis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3445-3445
Author(s):  
Magnus Moksnes ◽  
Fredrik H. Schjesvold
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Induction Therapy ◽  
Research Funding ◽  
Response Analysis ◽  
Cell Transplant ◽  
First Line ◽  
Induction Regimen ◽  
Final Response ◽  
Group 1

Abstract Introduction: The use of triple agent induction therapy before first line high-dose therapy (HDT) and autologous stem cell transplant (ASCT) in multiple myeloma is now considered standard of care. While thalidomide/bortezomib/dexamethasone (VTD) is the only induction regimen approved by EMA, both cyclophosphamide/bortezomib/dexamethasone (VCD) and lenalidomide/bortezomib/dexamethasone (RVD) are recommended in the most recent ESMO guidelines (Moreau et al., Annals of Oncology, 2017). Prospective comparisons of VCD and RVD are lacking. Cross-study comparisons show that the combinations of proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) have the highest response rates (Malankody Nat Rev Clin Onc 2015). In recent years there has been a shift in choice of induction therapy from the VCD to the RVD regimen in our region. We have evaluated how this shift has affected depth of response 3 months after ASCT in all patients receiving first line HDT with ASCT in our region from January 1st, 2015, and how frequently our patients needed to change induction regimen, based on choice of first line therapy. Methods: All patients receiving first line HDT with ASCT for multiple myeloma in our institution in the period from January 1st, 2015 to March 16th, 2018 were evaluated for the final analysis of response 3 months post-ASCT. The induction regimen was chosen at their local physician´s discretion. The patients received 3-5 cycles of induction therapy before leukapheresis, HDT (melphalan 200mg/m2) and ASCT. All patients received a follow-up consultation in our institution 3 months post-ASCT, where response was evaluated and recorded according to the IMWG 2016 response criteria. No patients had started maintenance therapy at the time of evaluation. Age, sex, date of ASCT, the presence of high-risk cytogenetics, ISS stage at diagnosis, choice of induction regimen and response 3 months post-ASCT was recorded by the primary investigator (Table 1). In case of change of regimen during induction treatment, the reason was recorded. Patients receiving either VCD or RVD as induction therapy, who did not change regimen during induction, were included in the final response analysis. Results: 212 patients received HDT with ASCT in the period. 209 patients were evaluated 3 months after ASCT as of June 21st, 2018. 57.5% (122 patients) received VCD as first-line induction therapy, while 25.9% (55 patients) received RVD. 11.5% (14 patients) in the VCD group changed induction therapy vs 3.6% (2 patients) in the RVD group. Reasons for changing regimen were: not achieving at least a partial response (PR) (n=10), unacceptable toxicity (n=4), lack of documented reason (n=2). In the RVD group, 1 patient died from sepsis 2 weeks post-ASCT, and 1 patient refused to attend the post-ASCT evaluation. Therefore, 108 patients in the VCD group and 51 patients in the RVD group were included in the final response analysis. 29 patients could not confirm a complete response (CR) due to lack of bone marrow and/or serum immunofixation at response evaluation. For that reason, patients achieving CR, unconfirmed CR and very good partial response (VGPR) were compounded to a ≥VGPR response grade. In the RVD group 94,1% (48 patients) achieved ≥VGPR vs 85,2% (92 patients) in the VCD group. Similar differences were also present for confirmed CR (25% vs 18%) and unconfirmed CR (44% vs 35%). In addition, 2% in the RVD group (1 patient) achieved PR, while 3.9% (2 patients) had disease progression (PD) 3 months after ASCT. In the VCD group, 13.0% (14 patients) achieved PR, while 1.8% (2 patients) had PD 3 months after ASCT (Table 2, Figure 1). Discussion: RVD induction therapy before HDT with ASCT yielded higher rates of at least VGPR compared to VCD induction (85,2% s 94,1%). The choice of RVD as first line induction therapy necessitated fewer changes of induction regimen due to insufficient response or unacceptable toxicities compared to VCD induction (3,6% vs 11,5%). The differences were not statistically significant, possibly because of too few patients. Still, our results support the trend in our region of choosing RVD as first-line induction for transplant-eligible patients. These results should be confirmed in larger patient materials, and in prospective studies. Updated data with approximately 35 additional patients, mainly receiving RVD induction, will be presented at the ASH annual meeting if our abstract is selected for presentation. Disclosures Moksnes: Shire: Consultancy. Schjesvold:Amgen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy; Bayer: Consultancy; Janssen: Consultancy, Honoraria, Research Funding; Oncopeptides: Consultancy; Abbvie: Honoraria; Adaptive: Consultancy; Novartis: Honoraria.

Role of autologous stem cell transplant after induction therapy with bortezomib-lenolidomide or bortezomib-thalidomide in newly diagnosed multiple myeloma patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8596-8596
Author(s):  
N. Shah ◽  
D. Weber ◽  
R. Orlowski ◽  
M. Wang ◽  
S. K. Thomas ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Highly Active

8596 Background: The introduction of novel therapeutic options with bortezomib and immunomodulatory agents in the up-front management of multiple myeloma (MM) has significantly improved induction response rates. However, the role of high dose chemotherapy and autologous stem cell transplant (ASCT) after induction with these highly active agents is not known, especially in patients with only a partial response to induction therapy. Methods: We conducted a retrospective review of 95 newly diagnosed MM patients treated with induction bortezomib-lenolidomide-dexamethasone (BLD) or bortezomib-thalidomide-dexamethasone (BTD) prior to ASCT. Responses were graded according to IMWG criteria. Results: 19 patients received BLD and 76 patients received BTD. All patients were conditioned with a melphalan-based regimen. Of the 19 patients who underwent induction with BLD, complete response (CR), very good partial response (VGPR) and partial response (PR) were achieved in 2 (11%), 8 (42%) and 9 (47%) respectively for an overall response rate (ORR) of 19/19 (100%). After ASCT, CR, VGPR and PR were achieved in 9 (47%), 5 (26%) and 5 (26%) respectively for a continued ORR of 21/21 (100%). Notably, 4/8 (50%) of patients with a VGPR after induction therapy with BLD improved to a CR after ASCT. 3/9 (33%) of patients with an initial PR to BLD improved to a CR and 1/9 (11%) with a PR improved to VGPR after ASCT. Of the 76 patients who underwent induction with BTD, CR, VGPR and PR were achieved in 6 (8%), 37 (49%) and 31(41%) respectively for an ORR of 74/76 (97%). 1 patient had stable disease and 1 patient had progressive disease. After ASCT, 27/76 (36%) achieved a CR, 30/76 (39%) a VGPR and 18/76 (24%) a PR for an ORR of 75/76 (99%). Of the patients who initially had a VGPR to BTD 16/37 (43%) improved to a CR while 5/32(16%)of PR patients improved to a CR and 9/32 (28%) of PR patients improved to a VGPR. Conclusions: Of the 40 patients who only achieved a PR after induction therapy with BLD or BTD, 16 (40%) had further improvement to a CR or VGPR after ASCT. Thus there is a significant benefit of ASCT in these patients who initially demonstrate relative resistance to induction therapy with highly active regimens. [Table: see text]

PK-Directed Intravenous Busulfan In Combination With High-Dose Melphalan and Bortezomib As Conditioning Regimen For Patients With Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5513-5513
Author(s):  
Stefan K Barta ◽  
Amitabha Mazumder ◽  
Jason Carter ◽  
Lawrence Almanzar ◽  
Richard Elkind ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Conditioning Regimen ◽  
High Dose ◽  
Cell Transplant ◽  
Treatment Dose ◽  
Gi Symptoms ◽  
High Dose Melphalan

Abstract Introduction High dose therapy followed by autologous hematopoietic stem cell transplantation (ASCT) has an established role in the treatment of patients with multiple myeloma (MM). The most commonly used conditioning regimen in this setting is high-dose melphalan (200mg/m2; Mel200), which has been shown to result in improved progression free (PFS) and overall survival (OS). Achievement of a complete response (CR) following ASCT is an indicator for freedom from relapse, as well as PFS and OS. The CR rate observed after Mel200 followed by ASCT is between 10-35%. There is evidence that the combination of busulfan (Bu) and melphalan (Mel) results in longer PFS and OS compared to Mel alone. Additionally, the use of bortezomib (Btz) during conditioning with either high dose Mel alone or the combination of Mel and intravenous (i.v.) Bu has shown to be both safe and to have promising efficacy. The objective of our trial is to assess whether the combination of PK-directed Bu, Mel and Btz (BuMelBtz) during conditioning for a first ASCT in MM patients is both safe and efficacious. Methods Patients aged 18-72 with multiple myeloma, who had 1) measurable disease, 2) received less than one year of prior myeloma-directed therapy, 3) adequate organ function and performance status, and 4) an indication for ASCT were eligible. Exclusion criteria were >/= grade 2 neuropathy, prior stem cell transplant, uncontrolled intercurrent illnesses or comorbidities, unresolved >/= grade 2 toxicities from prior therapies, and prior malignancies except non-melanoma skin cancer. Treatment consisted of PK-directed i.v. Bu (4 daily 3-hour infusions from day (D) -6 to -3 to target a total AUC of 20,000 μMxmin), i.v. Mel 140mg/m2 on D-2, and i.v. Btz 1.4mg/m2 on D-6, -4, +1 and +4. The individual daily doses for Bu on D-6 and D-5 were determined by PK measures following a test dose (0.8mg/kg) 5-9 days prior to first Bu treatment dose; the last 2 doses (day -4 and -3) could be adjusted following another PK measure after the first full treatment dose on D -6. Stem cells were infused on D0. Subsequent consolidative or maintenance therapy was left to investigator choice. Primary outcome was CR rate assessed on D +100 post ASCT as per IMWG criteria. Secondary outcomes were overall response rate (ORR), toxicities, PFS and OS. The trial is registered at clinicaltrials.gov (NCT01605032). Results To date, 13 patients have been treated. The median age was 63 years (range 44-70), 62% (n=8) were male, 23% had ISS stage 3 (3/13), no patient had high risk cytogenetic features. The median number of regimens prior to ASCT was 1 (range 1-3) and included bortezomib in 92% (n=12). Prior to BuMelBtz the best treatment response had been stable disease (SD) in 3 patients, partial response (PR) in 8; only 1 patient each had achieved a very good partial response (VGPR) or CR. Following BuMelBtz/ASCT, median days to ANC >/=0.5 x 109/L and platelet count >/=30 x 109/L were 11 (range 10-13) and 17 (11-29), respectively. The most common non-hematological toxicities were alopecia (100%), oral mucositis (62% G3), dysphagia (85% G3, but no patient required TPN or enteral feeding), as well as electrolyte abnormalities (62% G3/4). Other common toxicities were nausea (92%, all G1/2), diarrhea (84% G1/2, 8% G3), while 77% of patients developed fully reversible transaminitis (15% G3). Less common G3 toxicities included delirium (8%), colitis (8%), skin infection (zoster, 8%), other infections (23%), and delirium (8%). One patient developed GI symptoms suggestive of acute GVHD on a gastric biopsy 8 weeks after ASCT. No patient developed sinusoidal obstruction syndrome of the liver. At 100 days post BuMelBtz/ASCT, response assessment was available for 8 patients: 1 achieved a stringent CR (12.5%), 4 VGPR (50%), and 3 PR (37.5%), resulting in a 100% ORR. One patient improved from a VGPR to a stringent CR during follow up. After a median follow up of 5 months (range 1-15) all patients are alive and no patient has relapsed. The trial is ongoing. Conclusion PK directed i.v. Bu in combination with Mel and Btz (BuMelBtz) is an effective and safe conditioning regimen for patients with multiple myeloma. Further evaluation is warranted. Disclosures: Barta: Otsuka: Research Funding; Onyx: Honoraria, Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Honoraria. Off Label Use: IV Busulfan for the treatment of multiple myeloma.

Bortezomib Plus Melphalan and Prednisone as Induction Prior to Transplant or as Frontline Therapy for Non-Transplant Candidates in Patients with Previously Untreated Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3325-3325
Author(s):  
Cristina Gasparetto ◽  
Jon P Gockerman ◽  
Louis F Diehl ◽  
Carlos de Castro ◽  
Joseph O Moore ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Partial Response ◽  
Induction Therapy ◽  
Stem Cell Mobilization ◽  
Gm Csf ◽  
Best Response ◽  
Frontline Therapy ◽  
Cell Mobilization

Abstract High-dose therapy plus autologous stem cell transplant (ASCT) is the standard of care for patients with multiple myeloma (MM) aged ≤65 years. Melphalan–prednisone (MP)-based therapy is the standard for non-ASCT candidates but is not typically used for transplant-eligible patients as prolonged therapy with melphalan can adversely affect stem cell collection. The phase 3 VISTA study demonstrated the superior efficacy of bortezomib plus MP (VMP) versus MP in previously untreated MM patients ineligible for ASCT. In this phase 2 study, we evaluated the efficacy of a shorter course of VMP on a different treatment schedule as induction therapy prior to ASCT or as frontline therapy in non- ASCT candidates. Patients aged ≥18 years with previously untreated MM received up to six 28-day cycles of bortezomib 1.3 mg/m2 IV, days 1, 4, 8, and 11, plus oral melphalan 6 mg/m2 and oral prednisone 60 mg/m2, days 1–7. After 2–6 cycles, ASCT-eligible patients could proceed to stem cell mobilization (G-CSF 10 mg/kg/day ± GM-CSF 250 mg/m2/ day or cyclophosphamide 4 g/m2 + GM-CSF) and conditioning with melphalan 200 mg/ m2 (140 mg/m2 if aged >65 years). Response was assessed every two cycles and post- ASCT by International Uniform Response Criteria. The primary end point was complete response (CR) rate to VMP. A total of 45 patients were enrolled; 27 were male. Median age was 63 years (range 33–75). MM subtype was 67% IgG, 16% IgA, and 9% each κ- and λ- light-chain; 37% of patients had ISS Stage III MM, 22% had ECOG performance status >1, and 70% had ≥40% plasma cells in bone marrow. In total, 20 patients proceeded to ASCT. Median duration of VMP was 4 cycles in both non-ASCT (range 1–6) and ASCT (range 2–6) patients. Response rate (best response) to VMP was 95% (42 of 44 evaluable patients), including 9% stringent CR (sCR), 9% CR (18% ≥CR [95% CI: 7%, 30%]), 27% very good partial response (VGPR), and 50% partial response (PR). Best response was achieved after cycle 2 in 10 patients, cycle 4 in 25 patients, and cycle 6 in 7 patients. All 20 ASCT patients had successful stem cell mobilization; median yield of CD34+ cells/ kg was 5.6 x 106 (range 2.3–12.2 x 106), in a median of 2 collection days. Post-transplant responses were 10% sCR, 20% CR, 55% VGPR, and 5% PR; the remaining 2 patients need further follow-up for response assessment. Response improved post-VMP to post-ASCT in 10 patients (6 PR to VGPR, 2 PR to CR, 2 VGPR to CR). After median follow-up of 14.0 months (range 7.4–47.7) and 14.6 months (range 8.2–42.9) in non-ASCT and ASCT patients, respectively, both median time to progression and progression-free survival were 19.8 months (95% CI: 14.3 months, not estimable [NE]) in non-ASCT patients and 27.9 months (95% CI: 14.6 months, NE) in ASCT patients. A total of 7 patients (5 non- ASCT, 2 ASCT) have died; 1-year survival rate was 82% (95% CI: 59%, 93%) in non- ASCT patients and 95% (95% CI: 69%, 99%) in ASCT patients. Most common grade 3/4 adverse events in all 45 patients during VMP therapy included peripheral neuropathy (24%), thrombocytopenia (20%), neutropenia (18%), and infection (9%). Only 1 patient had deep-vein thrombosis. In conclusion, VMP represents a highly effective therapy for previously untreated MM, with 45% of patients achieving VGPR or better, including 18% sCR/CR. Toxicities were predictable and generally manageable. Short-course VMP therapy did not negatively impact stem cell mobilization, supporting its use as induction therapy prior to ASCT. Very high post-transplant response rates were seen, with 85% of patients achieving ≥VGPR, including 30% sCR/CR. Since achievement of CR/VGPR is associated with improved long-term outcomes in MM, the preliminary outcome data presented here appear promising; however, longer follow-up is required.

scholarly journals Outcomes of retreatment with anti-PD-1 monotherapy after response to first course in patients with cutaneous melanoma

2020 ◽  
Vol 16 (20) ◽  
pp. 1441-1453
Author(s):  
Eric D Whitman ◽  
Emilie Scherrer ◽  
Wanmei Ou ◽  
Clemens Krepler
Keyword(s):  
Overall Survival ◽  
Retrospective Study ◽  
Partial Response ◽  
Real World ◽  
Cutaneous Melanoma ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Tumor Response ◽  
Advanced Melanoma

Aim: To determine outcomes of retreatment with anti-PD-1 monotherapy for melanoma. Materials & methods: This retrospective study included adults with unresectable cutaneous melanoma who achieved stable disease (SD) or better after anti-PD-1 monotherapy and were retreated with anti-PD-1 monotherapy after ≥90-day gap. We determined overall survival and real-world tumor response. Results: For 21 eligible patients, from retreatment initiation, median follow-up was 14.4 months (range, 2.6–34.5); median overall survival was 30.0 months (95% CI: 14.4–not reached); 1-year survival was 100% (95% CI: 100–100%); 2-year survival was 83% (48–96%). Of 16 patients with recorded best real-world tumor response, ten (63%) responded (complete/partial response); three achieved SD; three had progressive disease. Conclusion: Patients with advanced melanoma achieving SD/better after first-course anti-PD-1 monotherapy may benefit from retreatment.

scholarly journals Zdravljenje diseminiranega plazmocitoma na Kliničnem oddelku za hematologijo UKC Ljubljana z avtologno presaditvijo krvotvornih matičnih celic v letih 2014 in 2015.

2016 ◽  
Vol 85 (9) ◽  
Author(s):  
Samo Zver ◽  
Enver Melkić ◽  
Tanja Radevska
Keyword(s):  
Multiple Myeloma ◽  
Partial Response ◽  
Induction Therapy ◽  
Progressive Disease ◽  
Induction Treatment ◽  
Hematopoietic Stem ◽  
Treatment Mortality ◽  
Good Partial Response ◽  
Autologous Hsct ◽  
Overall Mortality

Introduction. In the period from 01.01.2014 to 31.12.2015 at Clinical Department of Hematology, University Medical Centre Ljubljana, we treated 73 multiple myeloma patients with first autologous  hematopoietic stem cell transplantation (HSCT).Methods and results. Age of patients ranged from 27 to 72 years with the median age of 60 years. Induction treatment at the time of diagnosis consisted of: VD (bortezomib, dexamethasone) 60/73 patients (82%), VCD (bortezomib, cyclophosphamide, dexamethasone)  10/73  patients (14%) and VTD (bortezomib, thalidomide, dexamethasone) 3/73 (5%)  patients. As part of induction therapy, patients received from 1 to 9 cycles of treatment. Response to induction therapy prior to HSC(hematopoietic stem cells) collection was as follows: CR(complete remission )7/73(10%), VGPR (very good partial response) 28/73(38%), PR (partial response) 23/ 73(32%), SD (stable disease) 11/73(15%) andPD (progressive disease) 4/73(5%) patients. Response to induction therapy immediately prior to autologous HSCT: CR9/73 (12%), VGPR32/73 (44%), PR17/73(23%), SD 8/73(11%) and PD6/73(8%) patients. Response to induction therapy and the first autologous HSCT at D+100 after HSCT: CR9/67 (13%), VGPR 34/67 (51%), PR 12/67 (18%), SD 3/67 (4 %) and PD 7/67 (10%) patients (in 6 patients data are missing, because they are not mature yet).  With single HSCT 63 patients were treated, while 10 patients received double or second HSCT. The overall mortality of patients treated during the  period from 01.01.2014 to 31.12. 2015 was 6/73 or 8.2%.Conclusions. The treatment of multiple myeloma with autologous HSCT remains the cornerstone of efficiency,as demonstrated by the increasing share of the most desired responses to treatment, ie. CR and VGPR. The treatment mortality rate was within expectation limits.

scholarly journals Efficacy and Safety Profile of Bortezomib Based Regimens for Treatment of Newly Diagnosed Amyloidosis: A Systematic Review of Literature

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5583-5583
Author(s):  
Muhammad Abdullah Yousaf ◽  
Muhaddis Ejaz Ahmad ◽  
Maaz Ahmed Yusufi ◽  
Hamza Hassan ◽  
Adeela Mushtaq ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Retrospective Study ◽  
Partial Response ◽  
Induction Therapy ◽  
Cochrane Library ◽  
Al Amyloidosis ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Efficacy And Safety

Introduction: For more than a decade, bortezomib (V) has become an integral part of initial treatment of AL amyloidosis It is cytotoxic to plasma cells. We report published literature on efficacy and safety of bortezomib based regimens in patients (pts) with newly diagnosed amyloidosis (ND-AL). Methods: Following PRISMA guidelines, we performed a comprehensive literature search for articles published after 2007 using Pubmed, Embase, Clinical Trials.gov, Cochrane Library and Web of Science. Initially, 649 articles were identified and after a thorough screening, we finalized 9 studies involving 213 ND-AL patients. Prospective (n=91) and retrospective (n=122) studies were included. MeSH terms and keywords were bortezomib and newly diagnosed AL amyloidosis. Results: Chemotherapy followed by HDCT versus frontline HDCT / ASCT: In a retrospective study involving 31 pts by Scott et al., with induction chemotherapy with V-based regimens (n=12), with non-V-based regimens (n=6) and frontline (n=13) high dose melphalan (HDM) therapy followed by autologous stem cell transplant (ASCT). Overall hematological response (OHR) and organ response (OR) rates in the entire cohort after ASCT were 77% and 58% respectively. OHR and OR were 92% & 75% in V-pretreated group and 69% & 54% in pts who received no treatment. The trend was similar for other responses (Table 1). In a clinical trial by Huang, X., et al., induction therapy with Vd (V in combination with dexamethasone) prior to HDM/SCT was compared with frontline HDM/SCT in 58 patients. The OHR, and complete response (CR) between Vd+HDM/SCT (20 evaluable pts) and frontline HDM/SCT (23 evaluable pts) groups were 85.7% versus 53.5% and 67.9% versus 35.7% respectively. All organs showed better response in Vd+HDM/SCT group (Table 1). Vd/CyBorD (Cyclophosphamide, bortezomib, dexamethasone) prior to ASCT: In a prospective clinical trial by Sanchorawala et al., 35 pts were given induction with Vd before HDM and ASCT. Among 27 evaluable pts, OHR was 100% with CR in 76.9% and very good partial response (VGPR) in 23% pts. In a study by Hong et al., 20 patients received induction with Vd or CyBorD prior to ASCT. OHR was 89% with CR in 55%, partial response (PR) in 10% and VGPR in 33%. 5-year overall survival (OS) was 80% and 5-year progression free survival (PFS) was 69%. Vd/CyBorD without ASCT: In a retrospective study by Zhao et al., 23 pts received Vd. OHR was 100% with CR in 44% and PR in 38.9% pts. Median overall survival (mOS) was 38 months and 3-year OS was 41-72%. OR was 25% with kidney being the organ showing response in maximum pts (84%). Kikukawa et al., reported 8 pts who received CyBorD, OHR was 100% with CR in 50%, PR in 25% and VGPR in 25% pts. 63% pts showed OR in heart and/or kidney. In a study by Huang, B., et al., Vd was given to 12 renal ND-AL pts and among 10 evaluable pts, OHR was 80% with CR in 50% and PR in 10%. mOS was 8.2 months and OR was 50%. Other Regimens: In a study by Lee et al., involving 19 pts, VMP (bortezomib, melphalan, prednisone) was given as induction therapy. OHR was 84% with CR in 37%, PR in 26% and VGPR in 21% pts. OS was 39% at 2 years and PFS was 8 months. OR was 53% with heart (50%) and kidney (40%). In a retrospective review by Chari et al., 9 pts were treated with a triplet regimen (V, cyclophosphamide or lenalidomide/thalidomide and d). OHR was 88% with CR in 22% and PR in 66% pts. OR was 77% with heart and kidney both at 44%. Conclusion: In ND-AL pts, V-based combination regimens are very effective and well tolerated as induction therapy, or when used as therapy prior to HDM/ASCT and this approach resulted in better outcomes when compared to frontline HDM/ASCT. Three drug combination therapy with V is effective. Kidney and heart were the major organs to show improvement with therapy. Novel combinations need to be studied in randomized prospective clinical trials. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

scholarly journals High Rates of Varicella Zoster Virus Antibody Seroconversion and Persistence after Administration of the Adjuvanted, Recombinant Varicella Zoster Vaccine in Multiple Myeloma Patients Undergoing Active Treatment

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 50-50
Author(s):  
Karen Sweiss ◽  
Gregory Sampang Calip ◽  
Damiano Rondelli ◽  
Pritesh Patel
Keyword(s):  
Multiple Myeloma ◽  
Varicella Zoster Virus ◽  
Active Treatment ◽  
Progressive Disease ◽  
Vaccine Dose ◽  
High Rate ◽  
Cell Transplant ◽  
Zoster Vaccine ◽  
Varicella Zoster

Multiple myeloma (MM) patients are predisposed to high rate of infectious complications, with viral infections and in particular varicella zoster virus infection having a more than 10-fold increased incidence compared to the general population. This risk increases with use of autologous stem cell transplant (ASCT), multiple lines of therapy for relapsed disease, and proteasome inhibitor (PI) or daratumumab treatment. An adjuvanted, recombinant vaccine, consisting of the varicella-zoster virus glycoprotein E antigen (Shingrix, GlaxoSmithKline; Triangle Park, NC) is now available but studies in MM patients have been limited to the post-ASCT setting. We aimed to analyze the initial seroconversion rates as well as persistence of seropositivity in our MM cohort undergoing active anti-myeloma treatment. We evaluated 85 MM patients undergoing active anti-myeloma treatment who were tested at baseline for VZV antibody (Ab) status. Nine (10.6%) patients were found to have high risk cytogenetics at diagnosis. The median number of prior lines of therapy was 1 (1-10), with 80 (94.1%) patients receiving a prior or current PI-based regimen, 66 (86.8%) receiving ASCT, and 15 (19.7%) receiving a prior or current daratumumab-based regimen. At the time of first vaccination, 35 (41.1%) patients were receiving post-ASCT immunomodulator (IMiD) maintenance. Seven (8.2%) patients had a prior history of VZV infection. 67 (78.8%) patients were actively receiving antiviral prophylaxis with either acyclovir or valacyclovir. To determine vaccine immunogenicity, we used an anti-VZV ELISA assay. Using this test, VZV Ab seropositivity was measured at baseline and after each of the 2 vaccinations. In the entire cohort, 41 (48.2%) patients were found to be VZV Ab negative at baseline. Multivariate modified Poisson regression models with adjustment for prognostic and clinical factors were used to estimate relative risk (RR) and 95% confidence intervals for baseline VZV Ab seropositive status. We identified ISS stage 2 (RR 0.31, 95% CI 0.21-0.61; p&lt;0.001) or 3 (RR 0.52, 95% CI 0.32-0.86); p=0.010) disease and prior/ current daratumumab (RR 0.35, 95% CI 0.13-0.95; p=0.04) as strong predictors of baseline VZV seronegativity; IMiD maintenance (RR 2.15, 95% CI 1.00-4.65; p=0.05) and prior shingles (RR 2.61, 95% CI 1.24-5.51; p=0.011) were associated with VZV seropositivity. Sixty-two (72.9%) patients received one vaccine dose, 49 (57.6%) received 2 doses, and 3 (3.5%) refused the vaccine. The median time between both doses was 84 (53-189) days. Overall rates of seropositivity increased after 1 (87.9%; p=0.0002) and 2 (92.6%; p=0.0001) doses. Seroconversion from a baseline negative to positive test was observed in 16 (76.2%) and 23 (95.8%) patients after 1 and 2 doses, respectively. One patient who received prior cytotoxic chemotherapy failed to seroconvert after 2 doses, and 4 patients lost VZV seropositivity after a median of 348.5 days from the second vaccination dose. In a multivariate model, we observed that progressive disease and daratumumab treatment during time from vaccination to follow up VZV testing predicted for loss of VZV seropositivity. Of 42 patients on acyclovir after receiving both doses, 18 (42.9%) discontinued acyclovir with all patients but one remaining seropositive at most recent follow up. We report the first real world experience of the use of the adjuvanted, recombinant zoster vaccine in MM patients receiving active treatment. We show a high rate of initial VZV seronegativity and were able to show significant seroconversion after a single vaccine dose. In fact, despite studies showing benefit in patients receiving a total of 4 doses, we observed high seroconversion rates using 2 doses. Finally, we report for the first time strong predictors of baseline VZV seronegativity and maintenance of seropositivity in MM patients, in particular treatment with daratumumab. On the other hand, PI treatment was not associated with baseline seronegativity or loss of seropositivity. This data confirms that post-ASCT vaccination would be the optimal time to vaccinate patients, in particular when patients are immunocompetent while in remission on maintenance. The benefit of administering the vaccine in patients undergoing daratumumab or other treatment for progressive disease was not shown here and continued antiviral treatment rather than vaccination is likely to be the ideal prophylaxis strategy. Disclosures Calip: Flatiron Health: Current Employment. Patel:Amgen: Consultancy; Janssen: Consultancy; Celgene: Consultancy.

scholarly journals Inferior Survival with Use of Autologous Stem Cell Transplant As Second-Line Therapy in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2026-2026 ◽  
Author(s):  
Cara A. Rosenbaum ◽  
Danny Luan ◽  
Paul J Christos ◽  
Roger Pearse ◽  
Danielle Guarneri ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Research Funding ◽  
Cell Transplant ◽  
Second Line ◽  
First Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Delayed Group

Background: Multiple myeloma (MM) remains incurable with eventual relapse and death occurring despite multiple lines of chemotherapy. Standard frontline therapy for MM has traditionally consisted of combinations of immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and dexamethasone followed by consolidation with high-dose melphalan and autologous stem cell transplantation (ASCT). A randomized trial using IMiD and PI-based induction demonstrated significant progression-free survival (PFS) benefit with upfront ASCT in consolidation compared to ASCT in second-line at relapse, but no OS benefit (Attal et al, NEJM, 2017). Delay of ASCT to second-line or beyond may in part be due to the aforementioned lack of OS benefit shown with upfront ASCT and increase of sustained deep responses, including MRD negativity, to novel frontline 3 and 4-drug regimens and continuation of therapy in the frontline. We performed a chart review comparing PFS1, PFS2, and overall survival (OS) of patients who underwent upfront ASCT as consolidation to those who received ASCT in the second-line after one relapse ('delayed ASCT'). The study was approved by the Institutional Review Board at Weill Cornell Medical College. Methods: 124 MM patients who underwent ASCT either as consolidation in first-line or delayed ASCT after relapsing on one prior treatment between 2010-2016 were included. Demographics and clinical parameters were extracted from the electronic medical record. PFS1, PFS2, and OS were calculated from date of diagnosis to first relapse, second relapse, and death, respectively. Patients were censored if lost to follow-up prior to experiencing the relevant event. PFS1, PFS2, and OS of patients receiving upfront ASCT were compared to those of patients receiving delayed ASCT. Log-rank tests were used to statistically evaluate differences between Kaplan-Meier PFS/OS curves. Cox proportional hazards models were used to calculate hazard ratios (HR) using upfront ASCT as the reference treatment. Results: Among the 124 patients, 93 underwent upfront ASCT as consolidation and 31 underwent delayed ASCT after relapsing on one prior line of therapy (Table 1). Induction regimens and pre-transplant therapies received are detailed in Table 1. Of the delayed group patients, 6 underwent ASCT directly without second-line induction and 25 as consolidation after second-line therapy. Patients receiving upfront ASCT had significantly longer median PFS1 compared to patients who received delayed ASCT (6.45 vs 1.25 years; P<0.001), with a HR of 0.18 (95% CI, 0.11-0.29) (Figure 1A). Median PFS2 in the upfront ASCT group was likewise significantly longer than in the delayed group (9.19 vs 3.69 years; P<0.001), with a HR of 0.31 (95% CI, 0.18-0.55) (Figure 1B). With a median follow-up of 6.0 and 5.8 years in the upfront and delayed groups, respectively, median OS was not reached in either group but trended towards prolonged survival with upfront ASCT (P=0.052), with a HR of 0.46 (95% CI, 0.20 to 1.03) (Figure 1C). Conclusions: In this cohort of 124 MM patients undergoing ASCT as consolidation in the upfront setting or delayed ASCT in second-line after relapse, upfront ASCT was associated with significantly improved PFS1 and PFS2, similar to findings by Attal et al. However, in that study, no difference in OS was seen between upfront and delayed groups, while our data, with longer follow-up, showed median OS trending towards significance. This has important implications as with use of novel induction regimens and maintenance therapy, ASCT is more commonly being delayed to early relapse in second-line or beyond. If transplant is intended to be used in the first few lines of therapy, our data show that delaying ASCT even to second-line has a significant negative impact on PFS. In addition, a shorter OS with delayed transplant was suggested although did not reach statistical significance, possibly due to small numbers or more patients with high-risk MM in the delayed group. It is also important to note the lack of daratumumab-based regimens which may have improved PFS/OS in either or both arms. Thus, our findings should be prospectively validated in a larger trial of ASCT as consolidation in first-line vs second-line or beyond using novel, monoclonal antibody-based regimens. Disclosures Rosenbaum: Janssen: Research Funding; Honoraria Akcea: Other: Accordant Health. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau. Van Besien:Miltenyi Biotec: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

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