Abstract only
8002
Background: Escalated BEACOPP and derivatives achieved superior time to treatment failure (FFTF) over COPP/ABVD, resulting in higher overall survival (OS) for advanced HL. However, ...later clinical trials have failed to confirm OS superiority over ABVD. Methods: Eligibility criteria: clinical stage III/IV HL, International prognostic score (IPS) ≥ 3, age<60. We compared ABVD (8 cycles) vs. BEACOPP (escalated 4 cycles ≥ baseline 4), without irradiation. Randomization was stratified for institution and IPS. Primary endpoint was EFS, defined as treatment discontinuation, no complete response (CR) after 8 cycles, progression, relapse or death. Additional endpoints were CR, progression free survival (PFS), OS, quality of life and secondary malignancies. Outcomes were reviewed by study coordinators to ensure consistency across pts. Results: From 2002-2010, 549 pts were randomized (ABVD 275, BEACOPP 274): stage IV 74%, PS 0, 1, 2: 34, 48 and 17%, B-symptoms 81%, median age 35.2y, males 75%. IPS was 4 or higher for 59% of pts. Histology reviewed no HL in 4 cases. CR was 83% in both arms. With a median follow-up of 3.8 yrs, EFS at 4 yrs was 63.7% vs. 69.3% (HR = 0.86, 95%CI=0.64 to 1.15, p=0.312). PFS at 4 yrs was 72.8% vs. 83.4% (HR = 0.58, 95%CI=0.39 to 0.85, p=0.005). OS at 4 yrs was 86.7 vs. 90.3 (HR = 0.71, 95%CI=0.42 to 1.21, p=0.208). Toxic deaths occurred in 6 and 5 pts, with early discontinuation (prior to cycle 5) in 12 & 26 pts, respectively. There were 5 crossovers to BEACOPP and 10 to ABVD. Second malignancies occurred in 8 ABVD and 10 BEACOPP pts (myelodysplasia/leukemia 2 and 4, lung 2 and 1, NHL 3 and 2, other 1 and 3); cumulative incidence curves did not differ significantly. Conclusions: The primary endpoint (EFS) was similar between treatment arms. However, more progressions/relapses were observed with ABVD, while early discontinuations were more frequent with BEACOPP. Nevertheless, even in this high-risk group, OS was not improved with BEACOPP. Additional considerations (treatment burden and cost, fertility issues, long term relapses and immediate and late morbidity) may guide physician/patient decisions toward ABVD or BEACOPP.
A number of treatment options are available for patients with relapsed Hodgkin's disease (HD). Radiotherapy, salvage chemotherapy, high-dose therapy (HDT) followed by autologous transplantation, and ...classical or nonmyeloablative conditioning followed by allogeneic transplantation can all be effective in patients with relapsed HD. Patients with early relapse after modern first-line chemotherapy, as well as patients with primary progressive disease, will be candidates for innovative approaches including nonmyelablative stem cell transplant (NST). Although initial results with NST look promising, more time and structured study of both HD and NST will be necessary to ultimately define the role of NST in this disease.
Introduction
Multiple Myeloma (MM) is a heterogeneous disease with a complex clonal and subclonal architecture with few recurrent mutations. The arrival of next-generation sequencing (NGS) has ...allowed us to have a deeper understanding of the disease. Due to that complexity and the low recurrence of “driver” mutations, the study of general mutational profile, copy number variation (CNV) and translocations is crucial to make an accurate diagnosis and prognosis. For that reason, a clinically validated NGS capture panel has been designed to analyze in a single assay all interesting genetic aberrations simultaneously including SNVs, indels, CNVs and chromosomal translocations.
Methods
In addition to genomic DNA (gDNA) from 33 healthy donors to create a robust baseline forCNV detection,we studied 161 DNA samples from 149 newly diagnosed MM patients enrolled in the GEM2012MENOS65clinical trial and treated homogeneously: gDNA from 149 BM CD138+ plasma cells and 12 paired cfDNA from peripheral blood samples obtained at diagnosis.
First, starting with 100 ng of gDNA and 200ng for cfDNA samples, a custom targeted NGS panel using SureSelect capture technology (Agilent) followed by NextSeq500 (Illumina) sequencing identified SNVs, indels, CNVs and the most relevant IGH translocations within 26genes involved with MM. The average sequencing depth was 609x across samples; and 98% of the targeted regions were sequenced with >200x. Second, NGS custom panel results were compared with FISH (n=88) and whole exome sequencing (SureSelect XT V6) (n=48) results. Both NGS panel and exome raw data were analyzed by DREAMgenics applying a custom bioinformatic pipeline. Finally, 5 discordant cases were followed-up by SNP-arrays.
Results
We have identified 408 exonic and non-synonymous variants. At least 1 oncogenic mutation was detected in 86% (128/149) of patients. NRAS was mutated in25% of patients, followed by KRAS(23%), BRAF(12%) DIS3(11%) and TP53(9%). Other interesting pathogenic mutations were identified in FGFR3 and HIST1H1E genes in 9% and 5% of patients, respectively.
In 92% (11/12) of cfDNA samples at least 1 oncogenic mutation was detected. For this 12 cases, paired samples (BM CD138+vscfDNA) were available. A total of 39 somatic mutations were identified in those cases. In cfDNA, 10 mutations were detected, and 5 were present in both samples. Furthermore, a mean decrease of 0.19VAF was observed in cfDNA (0.12; 0.01-0.48) vs plasma cells (0.31; 0.01-0.51).
Regarding to CNV, 1q gain was detected in 32% of patients (28/88), and 1p and 17p deletions in 17% (15/88) and 13% (11/88), respectively. Additionally, ATR and CRBN gene amplifications were detected in 22% and 16%, respectively. When these data were compared to FISH, a 75% of sensitivity and 91% of specificity was achieved by our method, with a PPV of 68% and a NPG of 93%.
Translocations were identified in 28% (25/88) of patients, including 7% (6/88)) t(11;14), 14% (12/88), t(4;14), and 1 patient t(14;16). We also detected t(6;14)(p21;q32) IGH/CCND3 in 3 patients that had also been described in MM.Translocations were detected with a 94% of sensitivity, 99% of specificity, with a predictive positive value of 94% and a predictive negative value of 99%. Importantly, NGS-based method revealed a t(10;14) in 3 patients that had not been identified by FISH, a new translocation implying the miRNA hsa-mir-4537.
Finally, the impact on PFS from FISH and NGS results was analyzed separately. PFS was similar for translocations and 17p deletions. However, 1p-detected by NGS showed a higher negative prognostic impact (p=0,006 vs p=0,127 by FISH)(Fig.1). Furthermore, our panel showed that 7% of patients (6/88) had a bi-allelic TP53 inactivation. Survival analysis showed that these patients relapsed significantly earlier than the others (p=0.028). Amplifications (≥4 copies) in 1q+could not identified with this panel.
Conclusions
Our custom NGS-based test allows in a single assay a more comprehensive study of the genomic landscape of MM patients by (a) detecting with a high sensitivity the most important and recurrent mutations and cytogenetic alterations, (b) identifying translocations and CNVs not previously detected by FISH and (c) identifying a double-hit MM patient. Additionally, cfDNA could be analyzed with this NGS strategy identifying molecular alterations in most of the patients.
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Oriol:Celgene: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy. Sureda Balari:Takeda: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; Roche: Honoraria; Sanofi: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Incyte: Consultancy; Celgene: Consultancy, Honoraria; BMS: Speakers Bureau; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau. de la Rubia:Janssen: Consultancy, Other: Expert Testimony; Celgene: Consultancy, Other: Expert Testimony; Amgen: Consultancy, Other: Expert Testimony; Ablynx/Sanofi: Consultancy, Other: Expert Testimony. Mateos:Oncopeptides: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity’s Board of Directors or advisory committees; PharmaMar-Zeltia: Consultancy; Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; Regeneron: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity’s Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees; Amgen: 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; Celgene: Consultancy, Honoraria, Membership on an entity’s Board of Directors or advisory committees. Blade Creixenti:Amgen: 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; Oncopeptides: Membership on an entity’s Board of Directors or advisory committees; Takeda: Membership on an entity’s Board of Directors or advisory committees. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Garcia-Sanz:Novartis: Honoraria; Janssen: Honoraria, Research Funding; Incyte: Research Funding; Gilead: Honoraria, Research Funding; BMS: Honoraria; Amgen: Membership on an entity’s Board of Directors or advisory committees; Pharmacyclics: Honoraria; Takeda: Consultancy, Research Funding. Martinez-Lopez:Novartis: Research Funding; BMS: Research Funding, Speakers Bureau; Incyte: Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Roche: Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Vivia Biotech: Honoraria; Altum: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties; Hosea: Membership on an entity’s Board of Directors or advisory committees, Patents & Royalties.
Abstract 1261
Allogeneic stem cell transplantation is a poorly standardized treatment. Reported outcomes vary markedly, partly due to differences in treatment procedures. The EBMT performed a survey ...among its member centers about their present strategies in preventing and treating graft versus host disease (GvHD). Seventy-three centers from 23 countries participated in this survey. The main prophylactic regimens used in transplantations with myeloablative conditioning were cyclosporine (CsA) + methotrexate (MTX) in 83%, CsA + mycophenolate mofetil (MMF) in 14 %, tacrolimus (tacro) + MTX in 6%, CsA alone in 8%, and tacro alone, tacro + MMF and ex vivo T-cell depletion (TCD) in 1% of the centers. The administration of CsA was initiated on day -6 (1%), day -3 (13%), day -2 (7%), day -1 (78%) or day 0 (1%). CsA was initially given as short i.v. infusions in 56% (twice daily 91%), continuous infusion in 39% and orally in 5% of the centers. The initial CsA dose was most commonly 3 mg/kg/day (49%); 1–2,5 mg/kg/day was given in 16%, 4–6 mg/kg/day in 31%, and 10–12,5 mg/kg/day in 4% of the centers. Further doses were then usually adjusted according to CsA concentrations (88%), measured from whole blood (81%) or serum (19%). When measured from whole blood, the target CsA concentrations at 1 wk post-Tx ranged from 80 to 400 (mean 230) ng/ml, and at 2–4 wks and 2 mths the ranges (means) were 95–400 (210) and 60–350 (200) ng/ml, respectively. The typical duration of CsA prophylaxis was 60–100 (32%), 120–150 (10%), 180 (54%), or 210–365 (14%) days. In 56% of the centers the estimated risk of relapse affected the length of prophylaxis. MTX was given in the dose of 15 mg/m2 on day +1 and 10 mg/m2 on days +3, +6, and +11 in 63% and without the last dose in 28% of the centers. There were 6 other variants. Leucovorin rescue was given in 43% of the centers with variable dose and timing. ATG was included in the prophylaxis for one or more subgroups (one center all patients) in 79%, alemtuzumab in 25%, corticosteroids in 10%, and TCD in 24% (one center all patients) of the centers. The main prophylactic regimens in reduced intensity transplantations (RIC) were CsA + MMF (67%), CsA + MTX (33%), CsA (23%), in vivo TCD (19%), tacro + MMF (10%), ex vivo TCD (3%), and tacro alone and tacro + MTX (1% each). ATG was used in some groups of patients in 73% of the centers. The development of chimerism affected the intensity of prophylaxis in 82% of the centers. All centers used corticosteroids as first line treatment of acute GvHD. The treatment was started at first signs likely to be caused by GvHD (17%) or for grade II or higher (83%). The decision to treat was based on clinical signs only in 70% of the centers while in 30% histological documentation was needed. The corticosteroid of choice was methylprednisolone (83%) or prednisolone (17%). The initial daily dose/kg was 1-1, 5 mg (19%), 2 mg (76%), 3 mg (6%), 5–10mg (3%), or 20 mg (1%), given in 1 (16%), 2 (69%), 3 (9%) or 4 (6%) doses, i.v. (79%) or orally (21%). The severity of aGvHD affected the initial dose in 53% and the organ manifestation in 27% of the centers. The dose per kg/day indicating corticosteroid resistance and need for second line treatment was 1mg (3%), 2 mg (72%), 4–5 mg (13%), or 10 mg or more (12%). The minimum time to confirm corticosteroid resistance was 2 (2%), 3 (11%), 4–5 (27%), 6–7 (44%), 10–14 (13%) or 21 (3%) days. The most widely used second line treatments were MMF (33%), anti-TNF antibodies (31%), other monoclonal antibodies (16%), ATG (27%), extracorporeal photopheresis (ECP, 14%), mesenchymal stem cells (7%), alemtuzumab (7%), pentostatin (5%) and “keep going with corticosteroids” (12%). The initial treatment for newly diagnosed chronic GvHD in patients with no ongoing immunosuppressive treatment was corticosteroid (57%), calcineurin inhibitor (CNI) + corticosteroid (38%), or CNI alone (10%). The minimum duration of first line treatment of chronic GvHD to allow the evaluation of efficacy was 2 wks or less (21%), 2–4 wks (12%), 1 mth (42%), 1,5-4 mths (21%), or 9–12 mths (4%). The most commonly used second line treatments were ECP (53%), MMF (36%), rituximab (12%), CNI (12%), mTOR inhibitors (9%), corticosteroids (8%), and tyrosine kinase inhibitors (6%). In conclusion, the present results show marked differences between centers in the prophylaxis and management of GvHD. These findings underline the need for standardization and prospective controlled studies in GvHD prevention and treatment.
No relevant conflicts of interest to declare.
Abstract 1630
The management of recurrent or refractory Hodgkin’s lymphoma (HL) remains challenging. Previous published data have suggested that infiltrating normal B lymphocytes in classic HL ...lesions may contribute to the survival of Hodgkin and Reed-Sternberg cells in vivo. The objective of this prospective, multicenter, phase II trial was to investigate the activity of an anti-CD20 monoclonal antibody, ofatumumab, in combination to a standard platinum-based salvage regimen, ESHAP (O-ESHAP) followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) for patients with classical HL failing to first line chemotherapy. Forty- five patients (25 M / 21 F, median age 34 years, range 18–66) were enrolled in the study between June 2010 and June 2012. Treatment consisted on three cycles of ESHAP plus ofatumumab 1,000 mg days 1 and 8 on first cycle and day 1 on second and third cycles. At the time of study entry, 66% of patients had III-IV Ann Arbor stage, 16% bulky disease, 18% B symptoms, 40% extranodal HL and 52% ≥3 involved nodal areas. We respect to response to first-line therapy, 46% patients had achieved a completed response (CR) and then relapsed, 6% had a partial remission (PR), whereas the remaining 48% were primary refractory. Eighty-one percent patients have received 3 cycles of O-ESHAP as scheduled, three patients 2, and five 1 cycle (1 patient due to toxicity, 1 patient’s decision, 2 HL progression, and 4 treatments ongoing). Grade 3–4 WHO hematological toxicity was observed in 16%, 19%, and 20% after cycles 1, 2, and 3, respectively. Non-hematological toxicity was reported in 32%, 10%, and 20%, respectively. Overall response (OR) rate was 63% (49% CR and 14% PR). Response to O-ESHAP according to prior response to first-line chemotherapy is shown in table 1. Adequate PBSCs collection was achieved in 94% mobilized patients. Twenty-six out of 33 patients have already proceeded to ASCT. Two patients died of neutropenic sepsis after ASCT and HL progression, respectively. Preliminary results of this ongoing trial suggest that addition of ofatumumab to ESHAP is safe and has a promising clinical activity in patients with relapsed/refractory HL candidates to ASCT.
Table 1Response to O-ESHAP according to previous response to first-line treatmentResponse to first-line chemotherapyRelapsed or partial response (n=17)Refractory (n=16)Response after O-ESHAPOR16 (94%)7 (44%)CR14 (82%)3 (22%)PR2 (12%)4 (22%)Refractory1 (6%)9 (56%)
No relevant conflicts of interest to declare.
Context: Evidence for the benefits of early palliative care (EPC) in patients with solid tumors is strong, but EPC has received scant attention in hematologic malignancies. Objective: To assess the ...benefits of outpatient-based EPC for symptom control in patients with multiple myeloma. Methods: Retrospective study of patients attending the Multiple Myeloma Palliative Care Clinic at our hospital in the year 2013 (February 1-December 31). The following symptoms were assessed at baseline and at three follow-up consultations using a Numerical Visual Scale (0 = no symptoms; 10 = worst possible): pain, anorexia, constipation, insomnia, nausea/vomiting, dyspnea, anxiety, and sadness. Physical and emotional symptom burden scores were calculated. Pain interference with general activity, sleep, and mood was also evaluated. Results: About 67 patients were included. The proportion of patients reporting moderate-to-severe pain (Numerical Visual Scale ≥5) decreased significantly from baseline to the final follow-up: worst pain decreased from 57% to 18% (P < 0.0001), whereas average pain fell from 24% to 2% (P < 0.0001). The percentage of patients reporting no pain interference increased significantly from baseline: general activity (52% vs. 82%; P = 0.0001), sleep (73% vs. 91%; P = 0.01), and mood (52% vs. 87.5%; P = 0.0001). Physical and emotional symptom burden also improved, with significantly fewer patients reporting depression (13% vs. 5%; P = 0.001). Most patients (86.6%) were alive and still attending the Multiple Myeloma Palliative Care Clinic at study end. Conclusions: These findings indicate that EPC is feasible in patients with multiple myeloma. Pain and other symptoms were well controlled.
Patients with malignant hematologic disorders undergoing bone marrow transplantation (BMT) may develop renal insufficiency. A study was undertaken to assess prospectively the subclinical renal ...function changes with radioisotopic methods in patients undergoing BMT for hematologic malignancies.
We studied 71 patients with normal renal function undergoing BMT for various hematologic malignancies, mostly leukemias. Conditioning included chemotherapy and 12 Gy (45 patients) or 13.5 Gy (26 patients) fractionated total-body irradiation (TBI). In 21 patients receiving 12 Gy TBI, the kidney dose was limited to 10 Gy using partial transmission blocks fabricated after renal opacification with nonionic, hypo-osmolar contrast medium. The glomerular filtration rate (GFR) and effective renal plasmatic flow (ERPF) were determined radioisotopically before conditioning and at 4, 12, and 18 months, using 51Cr ethylene-diamine-tetra-acetic acid and 131I ortho-iodo-hippurate, respectively. Renal insufficiency was defined as a decrease of ≥30% in GFR or ERPF compared with the baseline values. The potential influence of patient- and treatment-related variables on renal dysfunction was assessed.
At 4 (early) and 12–18 (late) months, a ≥30% GFR drop was observed in 54% and 49% of patients and a ≥30% ERPF drop in 44% and 34% of patients, respectively. After stepwise logistic analysis, a GFR reduction at 4 months correlated significantly with age (<40 years old, worse), TBI using kidney blocks (partial kidney shielding to 10 Gy was associated with a higher rate of renal dysfunction at 4 months compared with the full TBI dose), and days of aminoglycoside/vancomycin use. An ERPF drop at 4 months was independently related with the days of amphotericin use and days of prostaglandin E1 use (prophylaxis against hepatic venoocclusive disease). A GFR and ERPF reduction at 12–18 months correlated with days of amphotericin use and days of prostaglandin E1 use, respectively.
Early post-BMT renal dysfunction is associated with the administration of potentially nephrotoxic drugs. An inverse correlation with the prescribed TBI dose was observed; patients whose kidneys received 10 Gy through the use of partial shielding blocks had significantly greater renal dysfunction at 4 months. The administration of potentially nephrotoxic contrast agents used in radiotherapy treatment planning may be responsible for the latter observation. Prostaglandin E1 use correlated with a significant reduction in ERPF at both 4 and 12–18 months.
▪
Introduction:
Carfilzomib dosed at 56 mg/m2 twice a week in combination with dexamethasone (Kd) is a standard of care for RRMM after 1-3 prior lines (PL) based on the ENDEAVOR study. Later, the ...ARROW study showed Kd dosed at 70 mg/m2 weekly to be superior to Kd dosed at 27 mg/m2 twice a week on RRMM patients (pts) after 2-3 PL. On the other side, Cyclophosphamide is an alkylating agent that has been widely combined with proteasome inhibitors and immunomodulatory drugs in MM, improving their efficacy with a good safety profile.
In this phase 2 randomized study, we have compared Kd plus cyclophosphamide (KCyd) with Kd in RRMM after 1-3PL, both with K dosed weekly at 70 mg/m2.
Patients and methods:
RRMM after 1-3 PL of therapy were included in the trial. Consistently with the ENDEAVOR population, previous therapy with proteasome inhibitors was allowed but refractory patients were excluded.
Pts were randomized 1:1 to receive K at a dose of 70 mg/m2 iv on days 1, 8 and 15 plus dexamethasone at a dose of 20 mg PO the day on and the day after K plus/minus KCyd at a dose of 300 mg/m2 IV on days 1, 8 and 15 of each 28 days-cycle, as continuous treatment until progressive disease or unacceptable toxicity. The primary endpoint was PFS and key secondary endpoints included response rates, safety profile, and OS.
Results:
Between January 2018 and February 2020, 198 RRMM pts were included. 97 pts were randomized to KCyd and 101 to Kd. The baseline characteristics of the patients were well balanced between both groups. The median age was 70 years, and 70% and 28% of pts were older than 65 and 75. The median number of PL was one; 61% of pts had received 1 prior line. 94% and 92% of patients had been exposed to bortezomib in the KCyd and Kd and all of them were sensitive. 72% and 67% of patients had been exposed to IMiD's and 51% and 55% of them were IMiD's-refractory in the KCyd and Kd. Only 4 and 6 patients in KCyd and Kd, had received anti-CD38 antibodies being all refractory.
After a median f/u of 15.6 months, median PFS was 20.7 m and 15.2 m in KCyd and Kd (p=0.2). In pts after 1PL, median PFS has not been reached in any arm (p=0.4) and in patients after 2-3PL, KCyd resulted in a median PFS of 20.7 vs 11m for Kd (p=0.4). Of note, in the IMiD-refractory population, the addition of Cy to Kd resulted in a significant benefit in terms of PFS: 26.2 months vs 7.7 months in the Kd arm (p=0.01). OS is immature with 23 and 25 events so far in KCyd and Kd, respectively.
The ORR was 78% for KCyd and 73% for Kd: 20% of patients in both arms achieved at least complete response, 33% and 28% very good partial response, respectively, and 25% partial response in both arms. The MRD-ve rate was 4% and 5%.
As far as toxicity is concerned, neutropenia was the only hematological adverse event more frequently reported in KCyd compared with Kd, of any grade (24% vs 11%) and grade 3-4 (13% vs 7%). This did not translate into more infections and the rate was comparable in both arms (5% G3-4 in both arms). Thrombocytopenia of any grade and grade 3-4 occurred in 14%/1% and 18%/10% in KCyd/Kd. Cardiovascular events of any grade occurred in 22% and 30% of patients in KCyd and Kd. Nine pts in KCyd developed G3-4 cardiovascular events, these included atrial fibrillation (1pt), cardiac failure (2 pts), myocardial infarct (2 pts), and hypertension (4 pts). In the Kd arm, 11 patients developed G3-4 cardiovascular events and consisted of hypertension in most of them (9 pts).
Conclusion:
Cyclophosphamide added to Kd 70 mg/m2 weekly in RRMM pts after 1-3 PL prolonged the PFS as compared to Kd particularly in the lenalidomide-refractory population. The administration of K at a dose of 70 mg/m2 weekly was safe and more convenient and overall, the toxicity profile was manageable in both arms.
Mateos:Abbvie/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Consultancy, Honoraria; PharmaMar-Zeltia: Consultancy; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: 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; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ocio:Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Asofarma: Honoraria; Sanofi: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Honoraria; GSK: Consultancy; MDS: Honoraria; Secura-Bio: Consultancy; Oncopeptides: Consultancy. Sureda Balari:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria; Merck Sharpe and Dohme: Consultancy, Honoraria, Speakers Bureau; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria; BMS: Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Honoraria; Gilead/Kite: Consultancy, Honoraria. Oriol:Celgene/Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Janssen: Consultancy; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees. Rosinol Dachs:Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria. Blade Creixenti:Takeda: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. San-Miguel:Amgen, BMS, Celgene, Janssen, MSD, Novartis, Takeda, Sanofi, Roche, Abbvie, GlaxoSmithKline and Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees.
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