Prognostic Factors Affecting Progression Free Survival For Multiple Myeloma Patients Receiving Lenalidomide Maintenance After Autologous Transplantation. Follow-Up Analysis Of The IFM 2005-02 Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3312-3312
Author(s):  
Gerald Marit ◽  
Valérie Lauwers-Cances ◽  
Denis Caillot ◽  
Thierry Facon ◽  
Cyrille Hulin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Board Of Directors ◽  
Maintenance Treatment ◽  
Autologous Transplantation ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Factors Affecting

Abstract Background Lenalidomide is an effective agent for the treatment of multiple myeloma (MM). The IFM Group conducted a randomized double-blind placebo controlled trial investigating the efficacy of lenalidomide maintenance treatment after autologous transplantation (IFM 2005-02 trial). The results showed that lenalidomide maintenance therapy significantly prolonged progression-free survival (PFS). Methods The aim of the present study was to identify prognostic factors affecting PFS in the 614 patients enrolled in this study. Analysis was performed using an extended Cox model, complete response (CR) was entered into the model as a time varying covariate. Results With a median follow-up of 60.6 months (54.5-68) PFS since randomization was shorter in the placebo arm (23.8 months, 95% CI 21-27.3) than in the lenalidomide arm (45.6 months, 95% CI: 40-55.1) (p<.001). Multivariate analysis showed that lenalidomide maintenance treatment arm, female sex, and obtention of CR were favourable prognostic factors for PFS. Conversely, beta2microglobuline, deletion of chromosome 13 and induction treatment reinforced by DCEP were associated with reduced PFS. For patients not in CR before initiation of maintenance therapy lenalidomide arm improved significantly PFS. This advantage is still observed in the 129 patients in CR at time of initiation of maintenance treatment. Conclusion These results confirm that obtention of CR at any time during treatment is a major factor for improving PFS in MM patients receiving first-line treatment including autologous transplantation. In this setting our data and those of other studies seems to support that lenalidomide maintenance treatment could be an intereresting option for delaying progression. At this time the gain in PFS did not translate into an OS improvement Disclosures: Marit: janssen-cilag: Honoraria, upport for travel to meeting, meeting expenses, upport for travel to meeting, meeting expenses Other; celgene: support for travel to meeting, meeting expenses Other. Off Label Use: lenalidomide maintenance treatment after autologous transplantation in myeloma patients. Facon:Amgen: Membership on an entity’s Board of Directors or advisory committees; Britsol-Myers Squibb: Membership on an entity’s Board of Directors or advisory committees; Onyx: Membership on an entity’s Board of Directors or advisory committees; Millennium: The Takeda Oncology Company: Membership on an entity’s Board of Directors or advisory committees; Celgene: Membership on an entity’s Board of Directors or advisory committees; Janssen: Membership on an entity’s Board of Directors or advisory committees; Novartis: Membership on an entity’s Board of Directors or advisory committees. Hulin:JANSSEN: Honoraria; CELGENE: Honoraria. Moreau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Roussel:JANSSEN: Honoraria; CELGENE: Honoraria. Avet-Loiseau:JANSSEN: Honoraria, Speakers Bureau; CELGENE: Honoraria, Speakers Bureau. Attal:CELGENE: Honoraria, Speakers Bureau; JANSSEN: Honoraria, Speakers Bureau.

scholarly journals Efficacy of Daratumumab, Lenalidomide and Dexamethasone Versus Lenalidomide and Dexamethasone Alone for Relapsed or Refractory Multiple Myeloma Among Patients with 1 to 3 Prior Lines of Therapy Based on Previous Treatment Exposure: Updated Analysis of Pollux

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 489-489 ◽  
Author(s):  
Philippe Moreau ◽  
Jonathan L. Kaufman ◽  
Heather J. Sutherland ◽  
Marc Lalancette ◽  
Hila Magen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Statistical Significance ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Refractory Multiple Myeloma

Abstract Introduction: Daratumumab is an anti-CD38 IgGκ monoclonal antibody that has been combined successfully with lenalidomide and dexamethasone. The combination of daratumumab with lenalidomide and dexamethasone (DRd) has been compared with lenalidomide and dexamethasone alone (Rd) in patients (pts) with relapsed or refractory multiple myeloma (RRMM) in a randomized phase 3 study (Dimopoulos MA, et al. N Engl J Med 2016; in press). In a pre-specified interim analysis, the DRd combination demonstrated significantly longer progression-free survival (PFS) in addition to deep and durable responses compared with the Rd arm. We performed subgroup analyses to further examine these efficacy data according to prior treatment exposure. Methods: Pts who received ≥1 prior line of therapy were randomized (1:1) to Rd (lenalidomide: 25 mg PO on Days 1-21 of each 28-day cycle; dexamethasone: 40 mg PO weekly) with or without daratumumab (16 mg/kg IV qw for 8 weeks, q2w for 16 weeks, then q4w until progression). The primary endpoint was PFS. Pts who were refractory to lenalidomide were not eligible. All analyses were performed in pts who received 1 to 3 prior lines of therapy. Results: Median follow-up was 13.5 months. Pts who were lenalidomide-naive prior to the start of study treatment (DRd, n=226; Rd, n=219) demonstrated significantly longer PFS with DRd vs Rd (median: not reached [NR] vs 18.4 months; HR, 0.36; 95% CI, 0.25-0.52; P<0.0001), with estimated 12-month PFS rates of 83.0% vs 59.9%, respectively. ORR was significantly higher with DRd vs Rd (96% vs 79%), with ≥VGPR rates of 76% vs 47% and ≥CR rates of 44% vs 21%, respectively (P<0.0001 for all). In the lenalidomide-exposed subgroup (DRd, n=46; Rd, n=45), median PFS was NR in both treatment groups (HR, 0.49; 95% CI, 0.22-1.12; P=0.0826); estimated 12-month PFS rates were 84.1% vs 63.1%, respectively. ORR was higher with DRd vs Rd but did not reach statistical significance (87% vs 71%; P=0.0729); however, rates of ≥VGPR (78% vs 38%; P=0.0001) and ≥CR (44% vs 12%; P=0.0011) were significantly improved with DRd vs Rd, respectively. For bortezomib-naive pts (DRd, n=44; Rd, n=45), PFS was significantly longer with DRd vs Rd (median: NR vs 15.8 months; HR, 0.34; 95% CI, 0.13-0.86; P=0.0170), with estimated 12-month PFS rates of 85.4% vs 69.2%, respectively. ORR was significantly higher with DRd vs Rd (98% vs 82%; P=0.0158), with trends toward increased rates of ≥VGPR (74% vs 55%; P=0.0544) and ≥CR (42% vs 23%; P=0.0576). In the bortezomib-exposed pts (DRd, n=228; Rd, n=219), median PFS was NR in DRd vs 18.4 months in Rd (HR, 0.35; 95% CI, 0.24-0.50 P<0.0001); estimated 12-month PFS rates were 82.8% vs 58.7%, respectively. Significant differences in ORR (93% vs 77%), rate of ≥VGPR (77% vs 43%) and rate of ≥CR (44% vs 19%) were observed with DRd vs Rd, respectively (P<0.0001 for all). Among bortezomib-refractory patients (DRd, n=54; Rd, n=49), the PFS benefit of DRd compared with Rd was maintained (median: NR vs 10.3 mo, respectively; HR, 0.46; 95% CI, 0.25-0.85; P=0.0117; Figure). The estimated 12-month PFS rates were 70.8% vs 44.4%, respectively. Similar to bortezomib-exposed pts, ORR (92% vs 68%; P=0.0024), rate of ≥VGPR (75% vs 36%; P=0.0001), and rate of ≥CR (46% vs 13%; P=0.0003) were all significantly higher with DRd vs Rd for bortezomib-refractory pts. Updated data will be presented at the meeting. Conclusions: Among pts who received 1 to 3 prior lines of therapy, significantly longer PFS and higher ORR were observed with DRd vs Rd among pts who previously received bortezomib or were refractory to bortezomib or were lenalidomide-naive. Higher rates of deeper responses were observed in pts who previously received lenalidomide or bortezomib. Follow-up is ongoing to assess PFS in pts who received 1 to 3 prior lines of therapy and previously received lenalidomide. These results further strengthen the significant benefit of combining daratumumab with Rd for RRMM. Figure Progression-free Survival in Bortezomib-refractory Patients who Received 1 to 3 Prior Lines of Therapy Figure. Progression-free Survival in Bortezomib-refractory Patients who Received 1 to 3 Prior Lines of Therapy Disclosures Moreau: Janssen: Honoraria, Speakers Bureau; Novartis: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria. Kaufman:Pharmacyclics: Consultancy; Incyte: Consultancy; Novartis: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. Sutherland:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Lalancette:Celgene: Honoraria; BMS: Honoraria. Iida:Celgene: Honoraria, Research Funding; Janssen Pharmaceuticals: Honoraria, Research Funding. Prince:Janssen: Honoraria; Celgene: Honoraria. Cochrane:BMS: Other: Received sponsorship to attend international meetings; Novartis: Other: Received sponsorship to attend international meetings; Celgene: Other: Received sponsorship to attend international meetings; Takeda: Other: Received sponsorship to attend international meetings. Khokhar:Janssen: Employment. Guckert:Johnson & Johnson: Equity Ownership; Janssen: Employment. Qin:Janssen: Employment. Oriol:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Newly Diagnosed Multiple Myeloma (MM) Patients Treated With Lenalidomide Induction and Maintenance Show a Low Incidence Of Second Primary Malignancies (SPMs)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2074-2074
Author(s):  
Annamaria Brioli ◽  
Charlotte Pawlyn ◽  
Walter Gregory ◽  
Samantha Hinsley ◽  
Samantha Marshall ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Incidence Rate ◽  
Maintenance Treatment ◽  
New Drugs ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Non Invasive ◽  
To Receive

Abstract Introduction New drugs have significantly improved the outcome of MM patients (pts) increasing both progression free survival (PFS) and overall survival (OS). Among new drugs lenalidomide (LEN) due to its oral availability and favourable toxicity profile is an attractive option both as an induction and as a maintenance treatment, with different studies demonstrating its effectiveness. Long term therapy with LEN, however, has been associated with an increased risk of developing SPMs. Aims We are conducting a large phase III study to evaluate the use of LEN as induction and/or as maintenance therapy. The primary end points of the study are OS and PFS. Secondary end points are response and toxicity. Methods Pts are treated following an intensive or a non intensive pathway based on their eligibility for high dose Melphalan (HDM) and stem cell transplantation (ASCT) and are randomised to receive induction therapy with cyclophosphamide and dexamethasone combined with either LEN (CRD) or thalidomide (CTD). Pts failing to achieve an optimal response are randomised to receive additional therapy with cyclophosphamide, dexamethasone and bortezomib (CVD) or no extra therapy. Pts with minimal or no response will automatically receive further therapy with CVD. A randomisation between LEN maintenance and no maintenance is also performed. Data on the occurrence of SPMs are being routinely collected as part of safety assessment during all protocol phases and follow up. Analyses were performed on treatment actually received. Results As per cut off of the 23rd July, 2371 pts have undergone the induction randomisation, of which 2368 are eligible for the safety analysis; 794 pts entered maintenance randomisation. The median follow up is 1.36 years from initiation of the study and 1.06 years from maintenance randomisation. Localised skin cancer other than melanoma were considered as non-invasive SPMs. At the time of the present analysis 17 SPMs have been reported with a cumulative incidence rate of 0.7% (cumulative rate of 0.6% for invasive SPMs and 0.1% for non-invasive SPMs); four additional patients, reported as having a SPM, were excluded, after central review of the data, either due to a previous history of malignancy or because of the evidence of a pre-existing tumour other than MM at the time of study entry. The median age at the time of SPMs development is 72 years (range 61-92), and the median time from trial entry to development of SPMs is 11 months (range 2.1-27.0). The most common SPMs reported were squamous cell carcinoma (4 pts, 2 invasive and 2 non invasive), breast cancer (3 pts), colon cancer (2 pts) and prostate cancer (2 pts). No haematological SPM has so far been reported. One patient, treated according to the intensive arm with LEN both as induction and maintenance, was reported as having a suspect myelodysplasia (MDS) due to anaemia and thrombocytopenia 2.7 months after entering the maintenance randomisation. No clear histological sign of MDS was found and the values improved after stopping maintenance treatment; these data fit with treatment related toxicity and not with the development of a MDS, and the patient was excluded from this analysis. Ten out of 17 SPMs developed during maintenance treatment or follow up phase, with 7 patients having received LEN maintenance. Median time from maintenance randomisation to SPMs development is 7 months (range 2-20.6 months). The remaining 7 were diagnosed during or immediately after induction. About half of the patients (8/17) were randomised to receive LEN induction; 3 patients received LEN both as induction and as maintenance. Interestingly only one of those 3 pts had been treated according to the intensive arm. With a median follow up of 1.36 years the estimated incidence rate at 1 and 2 years are 0.70% (95% CI .40-1.22)and 1.17% (95% CI .70-1.96) respectively (Figure 1). Conclusions Our data do not confirm previous findings of an excess risk of SPMs in association with the use of LEN and HDM in presenting patients, with 12/17 pts developing SPMs treated on the non intensive pathway that does not contain HDM. Most importantly only 0.4% of the patients enrolled within the intensive pathway developed a SPM, with only 2 of them receiving LEN maintenance. Longer follow up will help to further elucidate the risk of LEN associated SPMs. On behalf of the NCRI Haemato-Oncology subgroup Disclosures: Brioli: Celgene: Honoraria. Off Label Use: The presentation include the use of Lenalidomide as induction and as maintenance treatment for newly diagnosed multiple myeloma patients. Cook:Janssen: Honoraria, Research Funding, Speakers Bureau. Cavo:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Onyx: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Bristol-Meyer Squibb: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Morgan:Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Millenium: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Merck: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Johnson and Johnson: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees.

Characteristics Of Multiple Myeloma Patients With 6-Year Or Longer Progression-Free Survival After a Single Autologous Transplant

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3366-3366 ◽  
Author(s):  
Kehinde U.A. Adekola ◽  
Qaiser Bashir ◽  
Nina Shah ◽  
Sai Ravi Pingali ◽  
Simrit Parmar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Cell Transplant ◽  
Advisory Committees ◽  
Free Survival ◽  
Autologous Transplant ◽  
Preparative Regimen

Background High dose chemotherapy followed by an autologous stem cell transplant (auto-HCT) is considered standard of care in patients with newly diagnosed multiple myeloma (MM). In a recent randomized trial, median progression free survival (PFS) after auto-HCT, with or without maintenance therapy was 46 and 27 months, respectively (McCarthy P et al. NEJM 2012). However, about 15% of patients are reported to have much longer PFS (Pineda-Roman M et al. Cancer 2008). Here we tried to identify the factors that may predict a long PFS after auto-HCT. Methods We performed a retrospective chart review of patients who received an auto-HCT for MM between January 2000 and March 2007. A total of 1135 patients underwent an auto-HCT during this period, and 194 patients (17%) had a minimum PFS of 72 months or longer after a single auto-HCT. The primary objective was to determine the variables associated with a long PFS and overall survival (OS). Results Patient characteristics and outcomes are shown in the attached Table. The median age at auto-HCT was 56 years, and the median time from diagnosis to auto-HCT was 7.5 months. Twenty-three (13%) patients had ≥ 10% plasma cells in the bone marrow at auto-HCT and only 9 patients (4.8%) had high-risk cytogenetic abnormalities. One-hundred and fifty (77%) patients received induction therapy containing either an immunomodulatory (IMiD) agent or a proteasome inhibitor (PI). At the time of the auto-HSCT, only 13 (6.7%) patients were in CR and 38 (19.6%) were CR or VGPR after induction therapy (Table). One-hundred and sixty three (84%) patients received mephalan alone as conditioning regimen. Eighty-one (42%) patients received post auto-HCT maintenance. Eighty (41%) patients achieved a CR, while 104 (54%) achieved CR + VGPR after auto-HCT. Six patients (3.1%) developed a second primary malignancy post- autologous transplant. After a median follow-up of 95.4 months, median PFS was 97.3 months and median OS has not been reached. The 10-year PFS and OS were 41% and 73% respectively. Use of melphalan alone as preparative regimen was associated with a longer PFS and OS (p=0.004 and 0.004, respectively). Achievement of CR after auto-HCT was associated with a longer PFS only (p=0.001), and the use of IMiD or a PI as induction was associated with a longer OS (p=0.01). Conclusion Approximately 17% patients achieved a median PFS of 6 years or longer after a single auto-HCT. The long PFS in this cohort may be associated with younger age, low incidence of HR cytogenetics, use of an IMiD or PI as induction therapy, relatively low disease burden at auto-HCT, transplant from the year 2000 onwards, achievement of CR in >40% and the use of melphalan alone as preparative regimen. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees.

Outcomes of autologous stem cell transplant (ASCT) in multiple myeloma from a tertiary cancer center in India.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17003-e17003 ◽  
Author(s):  
Bhausaheb Pandurang Bagal ◽  
Navin Khattry ◽  
Amol Dongre ◽  
Sadhana Kanan ◽  
Hari Menon ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Maintenance Treatment ◽  
Progression Free Survival ◽  
Cancer Center ◽  
Cell Transplant ◽  
Early Stage Disease ◽  
Free Survival ◽  
Post Transplant ◽  
Stage Disease

e17003 Background: ASCT is part of standard treatment in multiple myeloma (MM).We report the results of such transplants and evaluate the role of prognostic factors if any in our patients. Methods: Sixty-one patients who underwent ASCT between June 1993 and March 2010 were included. Twenty four patients received VAD like regimen. Nineteen patients received novel agent based therapies. Ten patients underwent cyclophosphamide based mobilisation while only G-CSF based mobilisation done in 51 patients. Stem cells were harvested from peripheral blood in all patients. Melphalan was used at 200 mg/m2 in 24 patients. Prognostic factors evaluated for overall (OS) and progression-free survival (PFS) were baseline hemoglobin and albumin, ISS stage, disease status at day 100 post transplant, use of maintenance treatment post transplant, response to first line chemotherapy, use of novel agents before transplant and time to transplant from diagnosis. Results: Median age was 46 years. Median baseline haemoglobin (Hb) and albumin were 9.7 g/dl and 3.9 g/dl respectively. At the time of transplant 36% were in complete remission (CR), 5% in very good partial response (VGPR) and 28% in partial remission (PR). Median time to engraftment of neutrophils and platelets was 12 and 17 days respectively. Grade III–IV oral mucositis was seen in 35%. Transplant related mortality was 8.0 %. The 5 year overall survival (OS) and progression free survival (PFS) were 73% and 33% respectively. OS was better for patients with pre-transplant Hb greater than 9.7 g/dl (P= .04) and those who achieved CR at day 100 post transplant (P= .03). Patients who received maintenance therapy showed trend towards better OS (P= .07). PFS was better for patients with baseline albumin greater than 3.9g/dl (P = .043), Hb greater than 9.7 g/dl (P = .027) and early stage disease by ISS staging system (P=.001). Conclusions: Our study confirms that ASCT in such patients is safe and effective. Baseline albumin and Hb, ISS stage, day 100 disease response and use of maintenance treatment are important prognostic factors affecting survival.

scholarly journals Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3747-3747
Author(s):  
Charlotte Doublet ◽  
Marie-Sarah Dilhuydy ◽  
Emmanuelle Ferrant ◽  
Pierre Feugier ◽  
Alexandra Fayault ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Board Of Directors ◽  
Research Funding ◽  
Progression Free Survival ◽  
Oncology Nurses ◽  
Advisory Committees ◽  
Free Survival ◽  
Daily Dose ◽  
History Of

Abstract Median age at diagnosis of chronic lymphocytic leukemia is 72 years. However, only few patients over 80 years of age are included in clinical trials, even in those devoted to unfit patients. In order to evaluate both efficiency and safety of venetoclax in this category of patients, we conducted a multicentric retrospective study and collected data from 77 CLL patients from 19 FILO centers who started venetoclax after 80 years of age. Median age at venetoclax initiation was 86 years old (81-97). 63% of patients had a history of heart disease, 62% had renal failure (moderate 59% and severe 3%) and 29% had a history of severe infections. Despite their comorbidities and a CIRS greater than 6 in 70% of cases, their autonomy was preserved with a median performans status of 1 (0-4). In this comorbid geriatric population, pretherapeutic geriatric assessment was only performed in a single patient. The median number of prior therapies was 2 (0-6) with an exposure to a BCR inhibitor in 56% of cases. 11q and 17p deletion were found in 39% and 30% of cases respectively, 39% of patients had a complex karyotype and 30% harbored a TP53 mutation. However, in this real life population, these prognostic factors were only performed in half of patients. IGHV mutational status was only available in 11 patients, and 83% of them had unmutated IGHV. At the time of venetoclax initiation, the tumor lysis syndrome (TLS) risk was moderate in 57% of cases and high in 8% of cases. Venetoclax was administered as a single agent (42%) or in association with rituximab (58%). In total, half of the patients were hospitalized at each dose ramp-up, and only 3 patients were treated on outpatient basis. 82% of the cohort was able to reach the daily dose of 400mg. Half of the patients were included in a phone call monitoring program with oncology nurses to pre-emptively manage side effects and foster therapy adherence. The safety study reported 14% of TLS, with 2 discontinuations of treatment within the first month: one of which led to dialysis and the other to death. As in the previously published studies, 25% of patients had infectious complications, and grade 3 haematological and digestive toxicities were reported in 42% and 22% of cases, respectively. The reduction of the daily dose of venetoclax was necessary for 33%. Permanent discontinuation of venetoclax occurred in 40% of subjects, including 29% of early withdrawal (within the first 3 months). Main reasons for discontinuation were intolerance (21%), CLL progression (21%), death (21%) and scheduled treatment discontinuation (10%). The overall response rate was 86%, consisting of 49% of complete response (unconfirmed by bone marrow biopsy) and 37% of partial response. With a median follow-up of 21months, estimated progression free survival and overall survival were 29 and 38 months respectively. Prior exposure to a BCR inhibitor had no impact on progression free survival. To conclude, venetoclax has a manageable safety profile in elderly patients with comorbidities and can induce prolonged responses. Finally, if additional follow-up by oncology nurses seems to be more and more implemented, the pre-therapeutic onco-geriatric evaluation remains underexploited in this population. Disclosures Ferrant: AstraZeneca: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Other: Travel, Accommodations, Expenses. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Laribi: AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; AbbVie: Other: Personal Fees, Research Funding; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria.

scholarly journals Hispanic or Latin American Ancestry Is Associated with a Similar Genomic Profile and a Trend Toward Inferior Outcomes in Newly Diagnosed Multiple Myeloma As Compared to Non-Hispanic White Patients in the Multiple Myeloma Research Foundation (MMRF) CoMMpassstudy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4117-4117
Author(s):  
Louis Williams ◽  
Patrick Blaney ◽  
Eileen M Boyle ◽  
Hussein Ghamlouch ◽  
Yubao Wang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Latin American ◽  
Copy Number ◽  
African Ancestry ◽  
Progression Free Survival ◽  
Driver Mutations ◽  
Advisory Committees ◽  
Free Survival ◽  
Disease Biology

Abstract Introduction Large clinical data sets suggest that the natural history and prognosis of newly diagnosed multiple myeloma (NDMM) differs between patients of European and African ancestry, with the latter group exhibiting an earlier age at onset and poorer overall prognosis in some studies. The use of next generation sequencing (NGS) to characterize the genomic landscape of multiple myeloma (MM) suggests that the observed phenotypic differences between these groups of patients may reflect distinct underlying genomic profiles and mutational processes. Thus far, characterizations of this type have focused principally on patients of African ancestry (AA). Here, we characterize the genomic features and outcomes of a large series of patients of Hispanic or Latin American ancestry (HL) as compared to their Non-Hispanic white (NHW) counterparts. Methods Subjects were selected from the MMRF CoMMpass SM trial, a study that includes 1,154 patients with updated outcome data as of March, 2020. Within this data set, 760 patients had information on race and ethnicity. Among these, 55 HL patients and 478 NHW patients possessed complete clinical and genomic information. We analyzed baseline whole exome sequencing (WES) and long insert whole genome sequencing (WGS) as previously described (Walker, et al. Blood 2019). Our analysis focused on 63 known driver mutations in multiple myeloma and 39 sites of common copy number variation across the study population. Complex structural variants and tumor telomere length were called using previously described bioinformatic tools (Boyle et al. Leukemia 2021). Survival analysis was undertaken using the Kaplan-Meier method with hazard ratios determined by the Cox proportional hazards model. Results In a comparison of clinical features between the Hispanic and NHW population, we did not identify any differences in age of onset, gender, presenting cytogenetics, International Staging System Score (ISS), and IMWG Risk Category. The proportion of patients undergoing autologous stem cell transplantation was similar between groups. We identified no statistically significant differences in the presence of characteristic translocations involving IgH locus or in hyperdiploidy status. No statistically significant differences in tumor mutational burden or loss-of-heterozygosity percentage emerged between HL and NHW patients. We examined non-synonymous variations (NSV) and copy number variations at the loci of known MM driver genes and encountered no statistically significant differences in NSV, copy number, or biallelic status. We further categorized genes into pathways relevant to the pathogenesis of MM and discovered no difference in the proportions of patients harboring mutations in genes related to the MEK/ERK and NF-κB pathways, cell cycle regulation, and epigenetic modification. We were unable to the distinguish either population based on the presence of chromothripsis or in the overall preponderance of an APOBEC mutational signature. Tumor telomere length was not significantly different between the populations. An analysis of overall and progression free survival (PFS) with a median duration of follow up of 44 months revealed a trend toward poorer outcomes among the HL population that did not reach statistical significance. Median PFS was 24 months in HL patients and 35 months in the NHW population (p = 0.19). Median OS was not reached in either ethnic subgroup. In terms of overall survival, age, ISS score, overall number of driver mutations, and the presence of chromothripsis emerged with a negative impact on outcome (Figures 1a, 1b). These variables with the exception of chromothripsis retained their significant impact on progression free survival (Figure 2a, 2b). Conclusion The correlation between Hispanic or Latin American ancestry and underlying disease biology in MM has yet to be fully elucidated. In our analysis, which was based on self-declared ancestry as opposed to admixture, no obvious differences in significant measures of genomic variation known to impact prognosis in MM emerged between HL and NHW patients. These results may help to inform the future large-scale studies to ascertain the impact of genomics, disease biology and socioeconomic factors on outcomes in this heterogeneous patient population. Figure 1 Figure 1. Disclosures Walker: Bristol Myers Squibb: Research Funding; Sanofi: Speakers Bureau. Morgan: BMS: Membership on an entity's Board of Directors or advisory committees; Jansen: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees.

Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Prognostic Significance of Complete Response.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3126-3126
Author(s):  
Marta Krejci ◽  
Roman Hajek ◽  
Zdenek Adam ◽  
Ludek Pour ◽  
Lenka Zahradova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Complete Response ◽  
Advisory Committees ◽  
Term Survival ◽  
Free Survival ◽  
Different Response

Abstract Abstract 3126 Background: Autologous stem cell transplantation (ASCT) after high-dose melphalan 200mg/m2 has got an important role in the treatment of symptomatic multiple myeloma (MM). The prognostic significance of achieving complete response (CR) after ASCT was cause of great debate for a long time. Some studies have shown the strong prognostic significance of achieving CR in MM, but other studies have failed to correlation between strength of the response and outcome. Aim: In this report we describe the long-term outcome of cohort 232 MM patients (pts) after ASCT with aim to establish the actual prognosis for the different response categories and to analyse other factors that might predict for long-term survival. Methods: We evaluated 232 pts with newly diagnosed symptomatic MM who received ASCT as a part of the first-line treatment between 1995 and 2005, median follow-up from ASCT was 131 months (range 61–195). Results: Following ASCT, overall response rate was 90% (202/232), 23% (52/232) of pts were in complete remission (CR), very good partial response (VGPR) was achieved in 45% of pts (100/232), partial response (PR) in 22% of pts (50/232), minimal response (MR) or stable disease (SD) in 10% of pts (22/232). Median progression-free survival (PFS) and overall survival (OS) from ASCT were 30.8 and 71.9 months, respectively. Progression-free survival at 12 years after ASCT in different response categories was 41% for pts with CR, 11% for pts with VGPR and 10% for pts with PR. Overall survival at 12 years after ASCT was 51% for pts with CR, 22% for pts with VGPR and 20% for pts with PR. The achievement of CR after ASCT was independent factor for long-term survival, significance differences in OS and PFS were found between CR and non-CR groups (P under 0.001 and P under 0.001, respectively). On multivariate analysis, the other factors associated with significantly better OS were ISS stage under III (P = 0.002), no presence of renal impairment (P = 0.008), age under 60 years (P = 0.001), no presence of deletion 1q21 (P = 0.029) and lenalidomide treatment in the post-transplant relapse (P = 0.002). Conclusion: The achievement of complete response after ASCT in multiple myeloma is the most important prognostic factor, even after long-term follow-up. The relapse rate is low in patients who remained in CR after 12 years from ASCT. A long-term complete remission should be a goal of treatment. Disclosures: Hajek: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen Cilag: Honoraria.

Updated Follow-Up In The CLL2007FMP Trial Supports The Non Superiority Of The Association Fludarabine-Cyclophosphamide (FC) Plus Campath Compared To FC Plus Rituximab and Points Out The Importance Of Minimal Residual Disease, By 6-Color Flow Cytometry Technique, On Progression Free Survival

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2870-2870
Author(s):  
Pierre Feugier ◽  
Remi Letestu ◽  
Sylvie Chevret ◽  
Thérèse Aurran ◽  
Beatrice Mahe ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Residual Disease ◽  
Limit Of Detection ◽  
Progression Free Survival ◽  
Final Evaluation ◽  
Advisory Committees ◽  
Color Flow ◽  
Free Survival ◽  
Minimal Residual

Abstract Introduction CLL2007FMP (fit medically patients) is a Randomized Phase-III Trial conducted by the French Cooperative Group on CLL and WM (FCGCLL/WM) and the “Groupe Ouest-Est d'Etude des Leucémies et Autres Maladies du Sang” (GOELAMS), comparing FC plus Rituximab (FCR) to FC plus Campath (FCCam) in previously untreated fit patients with chronic lymphocytic leukemia (CLL). Early results showed that the FCCam regimen was associated with an unfavourable safety profile limiting significantly its use in this indication (Blood 2012). We present here the results of the extended follow up of the CLLFMP2007 trial, with particular emphasis on survival data, minimal residual disease (MRD) and late adverse events. Methods In this trial, 178 younger (<65) fit patients (pts) (cumulative illness rating scale (CIRS) score of up to 6), were enrolled between November 2007 and January 2009. Cases with del(17p) were excluded. Pts were randomly assigned to receive 6 oral courses of FCR (n=83) or FCCam arm (n=82). The primary endpoint of the study was 3-year progression-free survival (PFS). Secondary endpoints were safety, response to treatment, overall survival (OS) and MRD. MRD evaluation was performed by 6-color flow cytometry in an oligocentric manner. MRD testing was scheduled before therapy initiation and at final evaluation, (i.e. 3 months after completion of immunochemotherapy) where it was to be assessed for all responding patients in both peripheral blood (PB) and bone marrow (BM). Recruitment was interrupted in January 2009 after 165 pts had been randomized due to an excess of mortality in the FCCam arm. Results PFS and OS were not significantly different between the two arms. With a median follow-up of 55.5 months (interquartile range, 50-60), 57 pts in the FCCam arm were free of disease progression compared with 50 in the FCR arm, with a 3-year estimated PFS at 81% in both arms (p=0.80). Fourteen pts died in the FCCam arm (7 from progression and 7 from toxicity) and 9 died in the FCR arm (all from progression), with a 3-year estimated survival at 90% vs. 88% (p=0.85). PFS was significantly impacted by IGHV mutational status (p=0.001), Binet stage (p=0.0002) and MRD level. At final evaluation, MRD was established using the result in PB samples (available for 120 patients) and was determined in 103 pts by combining the results from blood and BM samples. Interpretation was based firstly on the use of the classical 10-4 threshold as reference and secondly on the limit of detection of the technique (0.7x10-5). In MRD-positive patients, the median PFS was 44.7 months (PB) whereas it was not reached in the group with MRD lower than 10-4 (p<0.0001, figure 1) ; similar data were found in MRD-positive PB+BM patients with a median PFS of 46 months whereas it was not reached in the group with MRD lower than 10-4 (p=0.002). No significant difference was found regarding OS but follow-up is still short for this evaluation. Similar results were observed when considering the limit of detection of the MRD technique (data not shown). Late toxicities (occurring after the final evaluation at 3 months after the end of treatment or at the ninth month when treatment was prematurely stopped) included : 1 bile duct cancer, 1 myelodysplastic syndrome, 1 transient ischemic attack, 1 lung adenocarcinoma and one prostate cancer in the FCR arm and 3 febrile neutropenia, 3 pneumonia (1 due to legionella), 1 pneumococcal sepsis, 1 bronchitis, 1 toxoplasma eye infection, 1 pyelonephritis, 2 herpes zoster, 1 acrodermatitis, 1 subdural hematoma, 1 autoimmune thrombocytopenia, 1 agranulocytosis, 1 autoimmune haemolytic anaemia in the FCCam arm. Conclusion Results of this extended follow-up of the CLL2007FMP trial confirm the absence of superiority of the FCCam regimen on OS and PFS. Interestingly, longer follow-up did not reveal a higher rate of late toxicity in FCCam arm, notably in terms of secondary malignancies; Similarly to early toxicity, late was adverse events were mainly infectious. Finally, MRD status determined by 6-color technique in PB and/or BM at post-treatment evaluation was predictive of PFS whatever the treatment arm. This finding is in line with recent reports in other studies pointing out to the powerful value of MRD as prognostic factor, supporting its use as PFS surrogate primary endpoint in clinical trials. Disclosures: Feugier: roche: Honoraria. Cazin:roche: meeting invitation Other, Membership on an entity’s Board of Directors or advisory committees; GSK: meeting invitation, meeting invitation Other, Membership on an entity’s Board of Directors or advisory committees.

scholarly journals Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy - Final Analysis from the Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1663-1663
Author(s):  
Rose Turner ◽  
Hang Quach ◽  
Noemi Horvath ◽  
Ian H Kerridge ◽  
Flora Yuen ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Research Funding ◽  
Progressive Disease ◽  
Progression Free Survival ◽  
Publicly Traded ◽  
Advisory Committees ◽  
Free Survival ◽  
Depth Of Response

Abstract BACKGROUND Survival rates in multiple myeloma (MM) have significantly improved in recent decades with the advent of high-dose chemotherapy conditioned autologous stem cell transplantation (ASCT) and the availability of novel agents for induction therapy (Kumar SK et al. Blood 2008). Failure to respond to front-line bortezomib-based induction therapy remains a significant clinical challenge in transplant eligible (TE) newly diagnosed multiple myeloma (NDMM), and is associated with poor outcomes with shortened progression free survival (PFS) and overall survival (OS) (Lee SE et al. Ann Hematol. 2014). In combination with immunomodulatory agents (IMiDs), carfilzomib, a second generation proteosome inhibitor, has been shown to be highly effective in the context of MM induction with high rates of negativity for minimal residual disease (MRD) and few dose limiting toxicities (Langren O et al. Leukemia 2019). The ALLG MM17 trial is a multicentre single arm study of carfilzomib-thalidomide-dexamethasone (KTd) in TE NDMM patients refractory or with suboptimal response to bortezomib-based induction therapy, designed to evaluate the efficacy of early response adaption with a switch to an intensive salvage strategy. METHOD Eligible patients included those with TE NDMM, aged 18 years and older, demonstrating sub-optimal response to bortezomib-based induction therapy (failure to achieve a minimal response after 2 cycles, partial response [PR] after 4 cycles, or disease progression within 60 days of completing induction). Salvage therapy consisted of 100mg daily oral thalidomide, with 20 mg of oral dexamethasone and 20mg/56mg of IV carfilzomib on days 1, 2, 8, 9, 15, and 16, with of each 28-day cycle. Following 4 cycles, patients in stringent complete response (sCR) proceeded to melphalan conditioned ASCT whereas those in less than sCR received a further 2 cycles of KTd prior to ASCT. Consolidation therapy consisted of a further 2 cycles of KTd, followed by maintenance 100mg daily thalidomide and 40mg weekly dexamethasone (Td) continuing until progressive disease, unacceptable toxicity, or 12 months of therapy. Primary objectives were to determine the overall response rate (ORR) and safety profile of treatment with KTd salvage therapy, with secondary objectives to determine the maximal depth of response, progression free survival (PFS), and overall survival (OS) achieved with sequential treatment with KTd salvage, ASCT, post-ASCT consolidation, and maintenance Td therapy. Efficacy assessments were performed via serum protein electrophoresis, serum free light chain and bone marrow evaluation. Next generation flow (NGF) cytometry MRD evaluation of bone marrow aspirate was undertaken pre-ASCT, at day 100 post-ASCT, after 2 cycles of consolidation KTd, and following completion of Td using standardized 8-colour EuroFlow platform. RESULTS 50 patients were recruited across 6 Australian sites between September 2016 and April 2018. Overall response rate to KTd salvage was 78% (Credible Interval 95%: 64.4-87.1%), with dual proof of concept criteria met (observed ORR ≥ 50% and posterior probability that the true ORR exceeds 30% is ≥ 0.90). Response rates included 12% sCR, 6% CR, 38% VGPR, and 22% PR. Sixteen patients discontinued treatment (32%) including 10 cases (20%) of progressive disease, and 2 patient deaths without progression. NGF MRD negativity was found to be 32%, 36% and 55% at the pre-ASCT, post-ASCT and post-consolidation time-points. At the cut-off date, estimated median follow-up for disease status was 38.6 months and median PFS and OS had not been reached. At 36 months PFS and OS were 63.9% (95%CI: 49.0 - 75.5%) and 79.9% (95%CI: 65.8 - 88.6%) respectively (Figure 1). KTd was found to be well tolerated with 44% of patients experiencing a grade 3 of higher adverse event (AE). Most common AEs included upper respiratory infection (48%), peripheral neuropathy (36%), musculoskeletal pain (32%), dyspnoea (28%), fatigue or lethargy (28%), and constipation (28%). Significant cardiac toxicity was not observed at this higher dose level of carfilzomib. CONCLUSION Results demonstrate that response-adaptive utilisation of KTd salvage, ASCT, and consolidation therapy induces high response rates, improving depth of response with high levels of sequential MRD negativity, and durable responses with an acceptable toxicity profile in TE NDMM patients failing bortezomib-based induction therapy. Figure 1 Figure 1. Disclosures Quach: Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Kalff: Amgen: Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Janssen: Honoraria; Roche: Honoraria; CSL: Honoraria; Sandoz: Honoraria. Bergin: Amgen: Other: Travel to workshop; Celgene: Consultancy. Reynolds: Novartis AG: Current equity holder in publicly-traded company; Alcon: Current equity holder in publicly-traded company; Abbvie: Research Funding. Spencer: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria.

A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 74-74 ◽  
Author(s):  
Jatin J. Shah ◽  
Edward A. Stadtmauer ◽  
Rafat Abonour ◽  
Adam D Cohen ◽  
William I. Bensinger ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Phase I ◽  
Board Of Directors ◽  
Dose Escalation ◽  
Research Funding ◽  
Progression Free Survival ◽  
Advisory Committees ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Grade 3

Abstract Abstract 74 Background: Carfilzomib, a novel proteasome inhibitor (PI), and pomalidomide, an immunomodulatory agent (IMiD), have both demonstrated promising activity as single agents or in combination with dexamethasone in relapsed/refractory multiple myeloma. IMiD+PI combinations including lenalidomide, bortezomib, dexamethasone and lenalidomide, carfilzomib, dexamethasone have had high response rates and good tolerability. We aimed to combine carfilzomib and pomalidomide with dexamethasone (Car-Pom-d) for the first time and hypothesized that this regimen would be highly active in patients with relapsed/refractory multiple myeloma. Here, we report the first findings from the Phase I dose-escalation and expansion portions of the first phase I/II trial of Car-Pom-d in patients with relapsed/refractory multiple myeloma (NCT01464034). Methods: The primary objectives were to determine the maximum tolerated dose (MTD) and the safety/tolerability of Car-Pom-d. Secondary objectives included determination of overall response rate, time to progression, progression free survival, and time to next therapy. All patients had to be refractory to prior lenalidomide, and must have been relapsed/refractory to their most recent therapy. Treatment consisted of 28-day cycles of oral pomalidomide once daily on days 1–21, intravenous (IV) carfilzomib over 30 minutes on days 1, 2, 8, 9, 15, and 16, and oral or IV dexamethasone 40 mg on days 1, 8, 15, and 22. Dose-escalation of carfilzomib started with 27mg/m2 carfilzomib/4mg pomalidomide/40 mg dexamethasone using a standard 3+3 schema based on dose-limiting toxicities (DLTs) occurring in cycle 1. Carfilzomib was initiated at 20 mg/m2for Cycle 1, days 1–2 at all dose levels. Investigators were permitted to adjust the dose of dexamethasone at any point based on their discretion. Adverse events (AEs) were graded by NCI-CTCAE v4. Response was assessed by the modified International Uniform Response Criteria. Results: In the Phase I dose-escalation portion of the trial, a total of 12 patients were enrolled from 6 centers. The median age was 61 years (range 44–78), 67% were male. The median number of prior regimens was 6 (range 2–15), and median time from diagnosis was 5.1 years. Four (33%) patients had prior stem cell transplant, 11 (92%) had prior bortezomib, and all were lenalidomide-refractory. Cytogenetic abnormalities included 5 patients with del(17p), 2 patients with t(4;14), and 1 patient each with del(13), t(11;14), and t(14;16). In these first 12 patients, drug-related AEs occurring in >20% of patients included fatigue (42%), anemia (33%), pneumonia (33%), dyspnea (25%), and thrombocytopenia (25%). Six (50%) patients experienced grade ≥3 AEs including 2 incidence each of neutropenia and febrile neutropenia. The MTD was established as the starting dose level (carfilzomib 20/27 mg/m2, pomalidomide 4mg, dexamethasone 40 mg). At this dose, 1 of 6 patients experienced a protocol-defined DLT of febrile neutropenia. At dose level 2 (carfilzomib 20/36 mg/m2, pomalidomide 4 mg, dexamethasone 40 mg), 2 of 6 patients experienced DLTs, consisting of grade 4 thrombocytopenia and grade 3 rash. All 12 patients were response evaluable with 2 very good partial response (VGPR), 4 partial response (PR), 2 minor response (MR), 2 stable disease (SD), and 2 progressive disease (PD) for a ≥ MR rate of 67%. The 6 month progression free survival was 70% (95% CI: 37 to 90%). Of the 5 patients with del(17p), 1 achieved VGPR, 2 achieved PR, 1 achieved SD. We then enrolled an expansion cohort of 20 patients from 8 centers resulting in a total study population of 32 patients, with 25 still receiving treatment. Three patients have died, all from progressive multiple myeloma. Early response assessments in 27 out of 32 patients show 2 VGPR, 7 PR, 6 MR, 8 SD, and 4 PD for a ≥MR rate of 56%. Conclusions: The Car-Pom-d regimen is well tolerated and achieves a high response rate in a heavily pre-treated, lenalidomide-refractory population with prior bortezomib exposure. Importantly, we have seen responses in patients with poor risk cytogenetics, specifically del (17p). We are beginning enrollment in a larger phase 2 cohort, and updated safety and efficacy data for all patients will be presented at the meeting. Disclosures: Shah: Celgene: Consultancy; Onyx: Consultancy; Novartis: Consultancy; Array: Consultancy. Stadtmauer:Celgene: Consultancy, Speakers Bureau; Millennium: Consultancy, Speakers Bureau. Abonour:Celgene: Honoraria, Speakers Bureau; Millenium: Honoraria, Speakers Bureau. Cohen:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Bensinger:Onyx: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau. Gasparetto:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kaufman:Millenium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; Onyx: Consultancy. Lentzsch:Celgene: Consultancy, Research Funding. Vogl:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium/Takeda: Consultancy, Research Funding; Otsuka: Consultancy; Acetylon: Research Funding. Orlowski:Onyx: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Research Funding. Durie:Onyx: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Amgen: Consultancy.

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