Nimustine Treatment of 11 Cases of Canine Histiocytic Sarcoma

ABSTRACT The objective of this retrospective study was to report treatment outcomes in dogs with histiocytic sarcoma (HS) that were treated with nimustine (ACNU). This study evaluated data from 11 dogs including 5 with macroscopic tumors that were treated in the primary setting and 6 that underwent aggressive local therapy while being treated in the adjuvant setting. The median ACNU starting dose was 25 mg/m2 (range, 20–30 mg/m2; 3- to 5-wk intervals, 1–8 administrations). The median overall survival in the primary and adjuvant settings was 120 days (median progression-free survival [PFS], 63 days) and 400 days (median PFS, 212 days), respectively. Neutropenia was observed in eight cases (grade 1, n = 1; grade 2, n = 2; grade 3, n = 2; grade 4, n = 3) with nadir neutrophil count at 1 wk after ACNU administration. Mild gastrointestinal toxicity (grade 1–2) was observed in three cases. ACNU was well tolerated and showed a similar outcome to that seen for lomustine, which is a drug commonly used to treat canine HS, in terms of overall survival and PFS in the current study population. Further investigations will need to be undertaken to definitively determine if ACNU is an appropriate alternative to lomustine for the treatment of HS.

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Thalidomide in Combination with Idarubicin, Dexamethasone and Etoposide (TIDE) Is an Effective Oral Combination in Heavily Pre-Treated Myeloma Patients.

Blood ◽

10.1182/blood.v110.11.4841.4841 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4841-4841

Author(s):

Mark D. Linch ◽

Matthew W. Jenner ◽

Sharon Dines ◽

Faith E. Davies ◽

Gareth J. Morgan

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Dose Reduction ◽

Median Overall Survival ◽

Response Rate ◽

Progression Free Survival ◽

Efficacy Data ◽

Free Survival ◽

Median Progression Free Survival ◽

Grade 3

Abstract Dexamethasone, thalidomide, etoposide and an antracycline have formed part of regimens such as DT-PACE which have demonstrated efficacy in previously treated patients with multiple myeloma. They are inpatient regimens which limit their usage in a palliative setting. We have designed an oral regimen incorporating these agents. The toxicity and efficacy data of this novel treatment are presented. Between October 2004 and May 2007 patients who had progressive myeloma or were intolerant of DT-PACE were treated with 100–200mg of thalidomide on days 1–21 and four days (D1–4) of 10mg/m2 idarubicin, 40mg dexamethasone and 50mg/m2 etoposide twice daily (TIDE). All agents were administered orally on a 21 day cycle for a maximum of 5 cycles. Aciclovir, co-trimoxazole and Lansoprazole were administered routinely and G-CSF was administered in the event of neutropenic fever and as secondary prophylaxis. Thromboembolism prophylaxis was not specified. Response was assessed using the international uniform response criteria for multiple myeloma. Toxicity was assessed using the CTCAE version 3.0. Efficacy data is presented as intention to treat. Nineteen patients received TIDE chemotherapy with a median age of 60 (range 36–70) and a male to female ratio of 11:8. Patients had a median of 3 (range 1–6) previous cycles and 18/19 patients had previous thalidomide. Patients received a median of 3 cycles (range 1–5) of TIDE. The most common grade 3/4 non-haematological toxicities were infection (8 patients), thromboembolism (3 patients), nephrotoxicity (2 patients), diarrhoea (1 patient) and peripheral neuropathy (1 patient). Grade 3–4 haematological toxicity occurred in 17/19 patients but 10/19 patients had grade 1–2 ‘toxicity’ at baseline. There were no recorded toxic deaths. Out of the 8 patients that suffered neutropenic fever, 7 experienced this on their 1st cycle resulting in treatment cessation in 3 patients. With prophylactic G-CSF or dose reduction, 3 of the remaining 4 patients did not get further neutropenic sepsis. In total 6 patients required a dose reduction and 17/19 patients had G-CSF. Seven patients were anti-coagulated from the beginning of this study; 2 were on Erythropoetin, 2 had previous thromboembolism and 3 were commenced at the clinicians discretion. None of the anti-coagulated patients went on to have a thromboembolic event. 18/19 patients were evaluable for response. The overall response rate was 42% (1CR, 7PR, 9SD and 1PD). The response rate to TIDE in patients who were intolerant of inpatient DT-PACE was the same as those that were treated with TIDE alone (50% vs 45%). The median progression free survival was 4 months (range 1–12) and the median overall survival was 8 months (range 1–31). In patients who responded to TIDE the median progression free survival was 7 months (range 3–12) and the median overall survival was 10 months (range 4–23). The TIDE regimen is able to induce responses in heavily pre-treated myeloma patients, including those taking thalidomide at the time of disease progression. Toxicities are acceptable but primary prophylactic G-CSF and anticoagulation should be contemplated. Consideration should also be given to using the TIDE regimen at an earlier stage in the disease process.

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Alternating versus continuous “FOLFIRI” in advanced colorectal cancer (ACC): A randomized “GISCAD” trial

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.3505 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 3505-3505 ◽

Cited By ~ 24

Author(s):

R. Labianca ◽

I. Floriani ◽

E. Cortesi ◽

L. Isa ◽

A. Zaniboni ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Experimental Studies ◽

Progression Free Survival ◽

Continuous Treatment ◽

Who Grade ◽

Free Survival ◽

Alternating Chemotherapy ◽

Grade 3

3505 Background: In ACC “FOLFIRI” is one of the standard regimens and is able to obtain about 40% response rate (RR) with an overall survival (OS) of 17–18 months. Experimental studies (Sobrero, 2000) indicate that an alternating chemotherapy could delay the appearance of cell resistance and reduce the therapeutic load for patients (pts). Methods: In order to evaluate whether intermittent “FOLFIRI” (CPT-11: 180 mg/sqm d1 + l-folinic acid -FA: 100 mg/sqm in 2 hr + 5fluorouracil-5FU: 400 mg/sqm bolus + 600 mg/sqm 22 hr infusion, d 1 and 2 every 2 weeks, for 2 months on and 2 months off) (arm A) was at least as effective as continuous “FOLFIRI” (same regimen, every month) (arm B), until progression in both arms, 336 pts from 27 Centers were randomised from 7/2001 to 6/2005. The characteristics of pts were: median age 64 years (r 29–75), males 214 (63%), PS 0: 222 (66%), liver mets only 166 (49%), multiple mts including liver 80 (24%). Results: RR was 29% in arm A and 35% in arm B, with a median progression-free survival (PFS) of 8.8 and 7.3 months respectively (HR = 1.00, 95% CI: 0.74 - 1.36). At a median follow-up of 27 months, median overall survival (OS), the primary endpoint of the trial, was 16.9 months in arm A and 17.6 in arm B (HR = 1.11, 95% CI: 0.83 - 1.48). Toxicity was acceptable and similar in the 2 arms (WHO grade 3–4 toxicity: neutropenia in 12% pts, diarrhoea in 11%, nausea/vomiting in 4% and fatigue in 3%). Conclusions: Our results demonstrate that alternating “FOLFIRI” obtains the same survival as a continuous treatment, thus reducing the discomfort to pts and the economic costs. No significant financial relationships to disclose.

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Efficacy and Safety of Bevacizumab Plus Erlotinib in Patients with Renal Medullary Carcinoma

Cancers ◽

10.3390/cancers13092170 ◽

2021 ◽

Vol 13 (9) ◽

pp. 2170

Author(s):

Andrew J. Wiele ◽

Devaki Shilpa Surasi ◽

Priya Rao ◽

Kanishka Sircar ◽

Xiaoping Su ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Progression Free Survival ◽

Medullary Carcinoma ◽

Tumor Burden ◽

Efficacy And Safety ◽

Free Survival ◽

Median Progression Free Survival ◽

Renal Medullary Carcinoma ◽

Grade 3

Purpose: To assess the efficacy and safety of bevacizumab plus erlotinib in patients with RMC. Methods: We retrospectively reviewed the records of patients with RMC treated with bevacizumab plus erlotinib at our institution. Results: Ten patients were included in the study. Two patients achieved a partial response (20%) and seven patients achieved stable disease (70%). Tumor burden was reduced in seven patients (70%) in total, and in three out of five patients (60%) that had received three or more prior therapies. The median progression-free survival (PFS) was 3.5 months (95% CI, 1.8–5.2). The median overall survival (OS) from bevacizumab plus erlotinib initiation was 7.3 months (95% CI, 0.73–13.8) and the median OS from diagnosis was 20.8 months (95% CI, 14.7–26.8). Bevacizumab plus erlotinib was well tolerated with no grade ≥4 adverse events and one grade 3 skin rash. Dose reduction was required in one patient (10%). Conclusions: Bevacizumab plus erlotinib is clinically active and well tolerated in heavily pre-treated patients with RMC and should be considered a viable salvage strategy for this lethal disease.

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Comparison of efficacy and tolerance of first-line palliative chemotherapy EOX and mDCF regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.3_suppl.135 ◽

2015 ◽

Vol 33 (3_suppl) ◽

pp. 135-135 ◽

Cited By ~ 1

Author(s):

Sebastian Ochenduszko ◽

Kamil Konopka ◽

Miroslawa Puskulluoglu ◽

Katarzyna Urbanczyk ◽

Andrzej Budzynski ◽

...

Keyword(s):

Overall Survival ◽

Median Overall Survival ◽

Palliative Chemotherapy ◽

Gastroesophageal Junction ◽

Locally Advanced ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Gastroesophageal Junction Adenocarcinoma ◽

Grade 3

135 Background: The aim of the study was to compare efficacy and tolerance of first-line palliative chemotherapy EOX (epirubicin/oxaliplatin/capecitabine) and mDCF (docetaxel/cisplatin/5FU/leucovorin) regimens in patients with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors. Methods: Each chemotherapy regimen was assigned with 21 patients. Planned treatment consisted of 12 every-two-weeks mDCF cycles (docetaxel 40 mg/m2 day 1, leucovorin 400 mg/m2 day 1, 5FU 400 mg/m2 bolus day 1, 5FU 1000 mg/m2/d days 1 and 2, cisplatin 40 mg/m2 day 3) or 8 every-three-weeks EOX cycles (epirubicin 50mg/m2 day 1, oxaliplatin 130mg/m2 day 1, capecitabine 1250mg/m2/d days 1 to 21). The primary endpoint was overall survival in all patients who commenced at least one chemotherapy cycle. Results: Median progression-free survival was 5.8 months in EOX group and 7.5 months in mDCF group (p=0.11), and median overall survival was 8.5 months and 12.0 months respectively (p=0.219). Due to toxicity, patients in the EOX arm had more frequent reductions of cytostatics doses (42.9% vs 5.0%; p=0.009) as well as delays in the administration of subsequent chemotherapy cycles (81.0% vs 65.0%; p=0.424). Rates of all grade 3 or 4 adverse events were comparable between both arms (76.19% in the EOX vs 70.0% in the mDCF; p=1.000). Toxicities that occurred more frequently in the EOX group compared to mDCF group were: nausea (28.6% vs 5.0%; p=0.093), thromboembolic events (19.0% vs 10%; p=0.663) and grade 3 or 4 neutropenia (71.4% vs 55.0%; p=0.443). Conclusions: In this patients population with locally advanced inoperable or metastatic gastric or gastroesophageal junction adenocarcinoma without overexpression of HER2 receptors treatment with mDCF regimen was associated with a statistically non-significant 3.5 month longer median overall survival without increase in toxicity. Updated data will be presented.

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Evaluation of efficacy and toxicity of nivolumab combined with or without docetaxel in patients with advanced NSCLC

Cancer Immunology Immunotherapy ◽

10.1007/s00262-021-02964-x ◽

2021 ◽

Author(s):

Yang Wang ◽

Jun Nie ◽

Ling Dai ◽

Weiheng Hu ◽

Jie Zhang ◽

...

Keyword(s):

Overall Survival ◽

Advanced Nsclc ◽

Objective Response ◽

Progression Free Survival ◽

Meaningful Improvement ◽

Free Survival ◽

Significant Difference ◽

Grade 3 ◽

Doublet Chemotherapy ◽

Platinum Doublet

Abstract Background The combination of PD-1/PD-L1 inhibitor and chemotherapy has been clinically confirmed to be beneficial as the first-line treatment of patients with advanced NSCLC. This study aimed to assess the effect of nivolumab + docetaxel versus nivolumab monotherapy in patients with NSCLC after the failure of platinum doublet chemotherapy. Materials and methods The efficacy and toxicity of nivolumab + docetaxel combination therapy versus nivolumab monotherapy were compared in this retrospective study. Primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), overall survival (OS), and toxicity. Results Between November 2017 and December 2019, 77 patients were included in this study, with 58 patients in the nivolumab group and 19 in the nivolumab + docetaxel group. The median follow-up was 18 months, and the PFS was 8 months for patients receiving nivolumab + docetaxel and 2 months for those receiving nivolumab alone (p = 0.001), respectively. Nivolumab + docetaxel showed superior OS compared with nivolumab, with the median OS unreached versus 7 months (p = 0.011). Among patients without EGFR/ALK variation, compared to nivolumab monotherapy, nivolumab + docetaxel showed better PFS (p = 0.04) and OS (p = 0.05). There was no significant difference in grade 3–4 adverse events (AEs) between the two groups (p = 0.253). Conclusions The combination of nivolumab and docetaxel demonstrated a meaningful improvement in progression-free survival and overall survival compared to nivolumab monotherapy, in patients with NSCLC after the failure of platinum doublet chemotherapy, irrespective of EGFR/ALK variation status.

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Use of nab-paclitaxel and gemcitabine in pancreatic cancer without granulocyte colony-stimulating factor: A multicenter real-world experience

Journal of Oncology Pharmacy Practice ◽

10.1177/10781552211038677 ◽

2021 ◽

pp. 107815522110386

Author(s):

Angela Chen ◽

Vincent H Ha ◽

Sunita Ghosh ◽

Carole R Chambers ◽

Michael B Sawyer

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Median Overall Survival ◽

Progression Free Survival ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Free Survival ◽

Colony Stimulating Factors ◽

Median Progression Free Survival ◽

Stimulating Factor

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

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Phase III Trial of Epirubicin Plus Paclitaxel Compared With Epirubicin Plus Cyclophosphamide As First-Line Chemotherapy for Metastatic Breast Cancer: United Kingdom National Cancer Research Institute Trial AB01

Journal of Clinical Oncology ◽

10.1200/jco.2005.01.1817 ◽

2005 ◽

Vol 23 (33) ◽

pp. 8322-8330 ◽

Cited By ~ 44

Author(s):

Ruth E. Langley ◽

James Carmichael ◽

Alison L. Jones ◽

David A. Cameron ◽

Wendi Qian ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Metastatic Breast Cancer ◽

Survival Time ◽

Metastatic Breast ◽

Progression Free Survival ◽

First Line ◽

Free Survival ◽

Grade 3 ◽

Line Chemotherapy

Purpose To compare the effectiveness and tolerability of epirubicin and paclitaxel (EP) with epirubicin and cyclophosphamide (EC) as first-line chemotherapy for metastatic breast cancer (MBC). Patients and Methods Patients previously untreated with chemotherapy (except for adjuvant therapy) were randomly assigned to receive either EP (epirubicin 75 mg/m2 and paclitaxel 200 mg/m2) or EC (epirubicin 75 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously every 3 weeks for a maximum of six cycles. The primary outcome was progression-free survival; secondary outcome measures were overall survival, response rates, and toxicity. Results Between 1996 and 1999, 705 patients (353 EP patients and 352 EC patients) underwent random assignment. Patient characteristics were well matched between the two groups, and 71% of patients received six cycles of treatment. Objective response rates were 65% for the EP group and 55% for the EC group (P = .015). At the time of analysis, 641 patients (91%) had died. Median progression-free survival time was 7.0 months for the EP group and 7.1 months for the EC group (hazard ratio = 1.07; 95% CI, 0.92 to 1.24; P = .41), and median overall survival time was 13 months for the EP group and 14 months for the EC group (hazard ratio = 1.02; 95% CI, 0.87 to 1.19; P = .8). EP patients, compared with EC patients, had more grade 3 and 4 mucositis (6% v 2%, respectively; P = .0006) and grade 3 and 4 neurotoxicity (5% v 1%, respectively; P < .0001). Conclusion In terms of progression-free survival and overall survival, there was no evidence of a difference between EP and EC. The data demonstrate no additional advantage to using EP instead of EC as first-line chemotherapy for MBC in taxane-naïve patients.

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Prognostic impact of prior local therapy in castration-resistant prostate cancer

Japanese Journal of Clinical Oncology ◽

10.1093/jjco/hyab019 ◽

2021 ◽

Author(s):

Mikifumi Koura ◽

Masaki Shiota ◽

Shohei Ueda ◽

Takashi Matsumoto ◽

Satoshi Kobayashi ◽

...

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Local Therapy ◽

Progression Free Survival ◽

Castration Resistant Prostate Cancer ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Castration Resistant ◽

Line Therapy

Abstract Objective This study aimed to reveal the prognostic values of prior local therapy in first-line therapy using androgen receptor-axis targeting agents (abiraterone or enzalutamide) or docetaxel for castration-resistant prostate cancer (CRPC). Methods The study included 303 patients treated with first-line therapy for non-metastatic and metastatic CRPC. The association between prior local therapy and therapeutic outcome including progression-free survival and overall survival was investigated by univariate and multivariate analyses as well as propensity score-matched analysis. Results In univariate analysis, local prior therapy was associated with a lower risk of all-cause mortality (hazard ratio, 0.56, 95% confidence interval, 0.40–0.79; P = 0.0009). Overall survival, but not progression-free survival, was better among patients with prior local therapy compared with patients without prior local therapy even after multivariate analysis and propensity score-matched analysis. Conclusions This study robustly indicated that prior local treatment was prognostic for overall survival among patients with CRPC. This finding is useful to predict patient prognosis in CRPC.

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Once-a-Week Versus Once-Every-3-Weeks Cisplatin Chemoradiation for Locally Advanced Head and Neck Cancer: A Phase III Randomized Noninferiority Trial

Journal of Clinical Oncology ◽

10.1200/jco.2017.74.9457 ◽

2018 ◽

Vol 36 (11) ◽

pp. 1064-1072 ◽

Cited By ~ 78

Author(s):

Vanita Noronha ◽

Amit Joshi ◽

Vijay Maruti Patil ◽

Jaiprakash Agarwal ◽

Sarbani Ghosh-Laskar ◽

...

Keyword(s):

Overall Survival ◽

Head And Neck ◽

Locally Advanced ◽

Progression Free Survival ◽

Phase Iii ◽

Absolute Difference ◽

Comparable Efficacy ◽

Advanced Head ◽

Adjuvant Setting ◽

Free Survival

Purpose Chemoradiation with cisplatin 100 mg/m2 given once every 3 weeks is the standard of care in locally advanced head and neck squamous cell cancer (LAHNSCC). Increasingly, low-dose once-a-week cisplatin is substituted because of perceived lower toxicity and convenience. However, there is no level 1 evidence of comparable efficacy to cisplatin once every 3 weeks. Patients and Methods In this phase III randomized trial, we assessed the noninferiority of cisplatin 30 mg/m2 given once a week compared with cisplatin 100 mg/m2 given once every 3 weeks, both administered concurrently with curative intent radiotherapy in patients with LAHNSCC. The primary end point was locoregional control (LRC); secondary end points included toxicity, compliance, response, progression-free survival, and overall survival. Results Between 2013 and 2017, we randomly assigned 300 patients, 150 to each arm. Two hundred seventy-nine patients (93%) received chemoradiotherapy in the adjuvant setting. At a median follow-up of 22 months, the estimated cumulative 2-year LRC rate was 58.5% in the once-a-week arm and 73.1% in the once-every-3-weeks arm, leading to an absolute difference of 14.6% (95% CI, 5.7% to 23.5%); P = .014; hazard ratio (HR), 1.76 (95% CI, 1.11 to 2.79). Acute toxicities of grade 3 or higher occurred in 71.6% of patients in the once-a-week arm and in 84.6% of patients in the once-every-3-weeks arm ( P = .006). Estimated median progression-free survival in the once-a-week arm was 17.7 months (95% CI, 0.42 to 35.05 months) and in the once-every-3-weeks arm, 28.6 months (95% CI, 15.90 to 41.30 months); HR, 1.24 (95% CI, 0.89 to 1.73); P = .21. Estimated median overall survival in the once-a-week arm was 39.5 months and was not reached in the once-every-3-weeks arm (HR, 1.14 [95% CI, 0.79 to 1.65]; P = .48). Conclusion Once-every-3-weeks cisplatin at 100 mg/m2 resulted in superior LRC, albeit with more toxicity, than did once-a-week cisplatin at 30 mg/m2, and should remain the preferred chemoradiotherapy regimen for LAHNSCC in the adjuvant setting.

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Melflufen and Dexamethasone in Heavily Pretreated Relapsed and Refractory Multiple Myeloma

Journal of Clinical Oncology ◽

10.1200/jco.20.02259 ◽

2020 ◽

pp. JCO.20.02259

Author(s):

Paul G. Richardson ◽

Albert Oriol ◽

Alessandra Larocca ◽

Joan Bladé ◽

Michele Cavo ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Overall Response Rate ◽

Response Rate ◽

Progression Free Survival ◽

Free Survival ◽

Duration Of Response ◽

Heavily Pretreated ◽

Grade 3

PURPOSE Melphalan flufenamide (melflufen) is a first-in-class peptide-drug conjugate that targets aminopeptidases and rapidly and selectively releases alkylating agents into tumor cells. The phase II HORIZON trial evaluated the efficacy of melflufen plus dexamethasone in relapsed and refractory multiple myeloma (RRMM), a population with an important unmet medical need. PATIENTS AND METHODS Patients with RRMM refractory to pomalidomide and/or an anti-CD38 monoclonal antibody received melflufen 40 mg intravenously on day 1 of each 28-day cycle plus once weekly oral dexamethasone at a dose of 40 mg (20 mg in patients older than 75 years). The primary end point was overall response rate (partial response or better) assessed by the investigator and confirmed by independent review. Secondary end points included duration of response, progression-free survival, overall survival, and safety. The primary analysis is complete with long-term follow-up ongoing. RESULTS Of 157 patients (median age 65 years; median five prior lines of therapy) enrolled and treated, 119 patients (76%) had triple-class–refractory disease, 55 (35%) had extramedullary disease, and 92 (59%) were refractory to previous alkylator therapy. The overall response rate was 29% in the all-treated population, with 26% in the triple-class–refractory population. In the all-treated population, median duration of response was 5.5 months, median progression-free survival was 4.2 months, and median overall survival was 11.6 months at a median follow-up of 14 months. Grade ≥ 3 treatment-emergent adverse events occurred in 96% of patients, most commonly neutropenia (79%), thrombocytopenia (76%), and anemia (43%). Pneumonia (10%) was the most common grade 3/4 nonhematologic event. Thrombocytopenia and bleeding (both grade 3/4 but fully reversible) occurred concomitantly in four patients. GI events, reported in 97 patients (62%), were predominantly grade 1/2 (93%); none were grade 4. CONCLUSION Melflufen plus dexamethasone showed clinically meaningful efficacy and a manageable safety profile in patients with heavily pretreated RRMM, including those with triple-class–refractory and extramedullary disease.

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