Pre-Phase Chemotherapy Followed By Ofatumumab (OFA) and Reduced Dose CHOP (OFA-mini-CHOP) for Patients over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – a Lymphoma Study Association (LYSA) Prospective Phase II Study (LNH09-7B)

Abstract Introduction: R-miniCHOP is the standard chemotherapy for patients over 80 years (y) with DLBCL. In the LNH 03-7B trial, the 2-year overall survival was 58.9% [95% CI: 49.3-67.2%]. Grade III/IV toxicity and deaths occurred during the two first cycles mainly (Lancet Oncol. 2011 May;12(5):460-8). In order to improve overall survival (OS) rituximab (R) was replaced by Ofatumumab (OFA), a humanised anti-CD20 monoclonal antibody. In vitro data suggest that OFA induces more potent complement-mediated cytotoxicity than rituximab, and clinical data demonstrate activity of OF in rituximab-refractory lymphomas). In addition, to reduce early toxicity a pre-phase (PP) with vincristine and prednisone (P) was tested. Patients and methods: Patients older than 80 y with untreated CD20+ DLBCL, Ann Arbor stage I to IV, left ventricular ejection fraction > 50%, and a performance status (PS) of 0 to 4 were eligible. Patients received a PP with vincristine (1 mg TD D-7) and P (60 mg TD D-7 to D-4) before the first cycle of OF-miniCHOP. PP was followed by miniCHOP chemotherapy (cyclophosphamide: 400 mg/m² D1; doxorubicine: 25 mg/m² D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m² by oral route from D1 to D5) plus OFA (1000 mg TD) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of PP OF-mini-CHOP as measured by the OS. Secondary endpoints were response rate (RR), progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented for all included patients on an intend-to-treat basis (n=120). Response to treatment was evaluated according to 1999 Cheson criteria. Results: From June 2010 to November 2011, One-hundred-twenty-patients (male, female) were included in 41 centers of the LYSA. The median age was 83 years (range 89-95). Seventy-seven percent of patients had a stage III/IV. LDH level was elevated in 58% of patients. Age-adjusted (aa) IPI was 2-3 in 57% of patients. One-hundred-twenty patients completed the PP, 107 the first three cycles and 89 received the whole regimen. For patients who started the first cycle, the mean relative Dose-Intensity during trial was 98%, 97% and 96 % for OFA, doxorubicine and cyclophosphamide respectively. Seventy-eight percent of patient received at least one injection of GCSF. The overall RR was 67.5%, including 35.8% of complete response and 20 % of unconfirmed complete response. At the time of this analysis, in September 2013, the median follow-up time was 26.6 months. The 2-year overall survival was 64.7% [95% CI: 55.3-72.7%]. The two-year PFS, EFS and DFS were 57.2% [95% CI: 47.7-65.6%], 53.1% [95% CI: 43.7-61.6%] and 66.6% [95% CI: 54.0-76.5%] respectively. Haematological toxicity was the most common side effect. Grade 3-4 neutropenia was observed in 20.8% of the patients and grade 3-4 thrombocytopenia in 1.7%. Seven patients (5.8%) experienced at least one episode of febrile neutropenia. Infusion reaction related to OFA was reported in 12.5% of patients. Prolonged hospitalization (> or = 10 days) was observed in 17 cases (14.1%) and mainly occurred during cycle 1 to cycle 3. Forty-five patients died during the treatment evenly distributed between lymphoma (62.2%), intercurrent and other causes (22.2%), and concurrent illness (15.6 %). No toxic death was reported. Six patients died during treatment (1 during PP, 4 during cycle 1 to cycle 3, 1 during cycle 4 to cycle 6) Thirty-nine patients died during follow-up. In univariate analysis, low aaIPI (0 /1) is the unique statistically significant prognostic factor of prolonged OS (OR 3.083, [1.458-6.517] CI95%). Instrumental Activities of Daily Living (IADL) score equal to 4 is associated with a longer PFS. By contrast, low Albuminemia level, undernutrition according to buzby index and high Charlson comorbidity index (CCI) were not predictive of survival. Conclusion: In DLCBL patients over 80 y, immunochemotherapy with PP OFA-mini-CHOP appears to be safe and effective, confirming that a substantial proportion of very old patients can be cured. The use of a PP seems to reduce the early death risk. OFA and PP seems to improve OS comparing with the previous reported data. The combination of a PP, monoclonal antibody against CD20 and miniCHOP can be the new standard regimen for DLBCL patients over 80 y. Disclosures Off Label Use: Use of ofatumumab in high grade lymphoma..

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Vinblastine, Mitoxantrone and Prednisone (MVP) Followed by Involved Field Radiotherapy (IF-XRT) for Early Clinical Stage Hodgkins’s Lymphoma: Long Term Follow-Up.

Blood ◽

10.1182/blood.v106.11.2677.2677 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2677-2677

Author(s):

Danielle Shafer ◽

Hossein Borghaei ◽

Michael Millenson ◽

Nicos Nicolaou ◽

Tahseen I. Al-Saleem ◽

...

Keyword(s):

Overall Survival ◽

Early Stage ◽

Survival Rates ◽

Complete Response ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Combined Modality Treatment ◽

Grade 3

Abstract Background: The treatment of early stage Hodgkin’s lymphoma (HL) continues to evolve in attempt to improve the safety profile of the regimens and decrease their long-term toxicities. Treatment related mortality exceeds that from HL after 12 to 15 years. In light of the potential long-term complications associated with irradiation and chemotherapy, particularly pulmonary and cardiac toxicity, alternative approaches minimizing exposure to drugs with long-term organ toxicity have been examined. Objectives: We evaluated a novel regimen of MVP and IF-XRT for non-bulky early-stage HL. The primary outcomes were response rate and freedom from disease progression. Secondary outcomes were toxicity, specifically pulmonary and cardiac dysfunction. Methods: Patients were enrolled in this multi-site phase 2 study between 1995 and 1999. Eligible patients were 18 years of age or older, had ECOG performance status 0–2 and pathologically confirmed, clinically staged non-bulky Stage I or II HL. Patients received a minimum of four cycles of mitoxantrone 8mg/m2 and vinblastine 6 mg/m2 intravenously on days 1 and 15 of each 28-day cycle. Prednisone 100mg was given orally days 1 to 5 and 15 to 19. Chemotherapy was continued for two additional cycles after complete response, up to eight cycles. Patients then received IF-XRT (30.6 Gy-39.6 Gy) four weeks after completion of chemotherapy. G-CSF was not used as primary prophylaxis. Results: Thirty-four patients were evaluated for response in a final review. A total of 32 patients (94%) achieved a complete remission after combined therapy. Thirty patients (88%) achieved a complete response after chemotherapy alone. At a median follow-up of 49 months (range 16.9–79.7 months), 10 patients had relapsed, and three deaths were documented. None of the deaths occurred during treatment. The median time to progression was 30 months. The overall survival and disease-free survival rates at 5 years were 90% (95% confidence interval [CI], 73–97%) and 78% (95% CI, 58–89%), respectively. The treatment was well tolerated without significant grade 3/4 toxicity. (Grade 3/4 leukopenia 18% of patients; neutropenia 28%) There were no significant changes in DLCO or left ventricular ejection fraction at 12 months observed after chemotherapy. Twenty-one patients received only 4 cycles of chemotherapy; the median dose intensity for the entire group was 85%. Conclusions: As the management of early-stage HL continues to evolve in attempt to reduce long-term toxicity, this trial serves as a reminder of the balance required between efficacy and toxicity in this largely curable population. In this relatively well-tolerated regimen, there was minimal long-term toxicity, but a high number of relapses, most of which were successfully salvaged with resultant excellent 5-year overall survival rates. As the treatment for early-stage HL moves forward, there will undoubtedly be further attempts to modify the ABVD backbone. We await those results as well as long term data from the German Hodgkin Study group investigating reduction of combined modality treatment (HD10) in a similar patient population.

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Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival

Journal of Clinical Oncology ◽

10.1200/jco.2013.52.0023 ◽

2014 ◽

Vol 32 (7) ◽

pp. 634-640 ◽

Cited By ~ 139

Author(s):

Antonio Palumbo ◽

Sara Bringhen ◽

Alessandra Larocca ◽

Davide Rossi ◽

Francesco Di Raimondo ◽

...

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Response Rate ◽

Complete Response Rate ◽

Progression Free Survival ◽

Complete Response ◽

Free Survival ◽

Grade 3 ◽

To Receive

Purpose Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma. Patients and Methods We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance). Results In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients. Conclusion Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.

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Rituximab - Inmunotherapy Combined with Chemotherapy, CHOP for the Treatment of Patients with Difusse Large B - Cell Lymphoma (DLBCL).

Blood ◽

10.1182/blood.v106.11.4745.4745 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4745-4745

Author(s):

Jorge H. Milone ◽

Fernando Bezares ◽

Maria del Carmen Ardaiz ◽

Dardo Riveros ◽

Luis Palmer ◽

...

Keyword(s):

Overall Survival ◽

High Risk ◽

B Cell Lymphoma ◽

Complete Response ◽

High Risk Group ◽

Hematologic Toxicity ◽

Gastric Bleeding ◽

Bulky Disease ◽

Free Survival

Abstract Several studies (GELA 98.5, MInT) have demonstrated the benefit of combination rituximab (R) with chemotherapy to improve event free and overall survival in patients with DLBCL. We analyzed retrospectively the safety of combination R-CHOP for 6 cycles (rituximab 375 mg/m2 day 1; cyclophosphamide 750 mg/m2 day 1; doxorrubicin 50 mg./m2 day 1; vincristine 1.4 mg/m2 day 1 and prednisone 100 mg/m2 day 1 to 5) the tolerance and adverse effects. We evaluated the response (R), event free survival (EFS) and the overall survival (OS). Between March to December 2004, 28 patients with DLBCL were evaluated, 17 men and 11 women, with a median age 57 years old (range 28 – 84). They were IPI low 21,4 %, low - intermediate 25%, high - intermediate 35,7 % and high risk 17,9 %. Elevated LDH was present en 14 patients, bulky disease > 7 cm in 50% of cases. During the treatment they presented hematologic toxicity grade III 21,4 % and grade IV 25% of cases; 1 patient had anaphilactic reaction; 2 patients pneumonia; 1 patient sepsis; 4 patients neutropenia and fever; and gastric bleeding 1 patient. Response was achieve in 71,4 %: complete response (CR) in 57,1%, parcial (PR) in 14.3 %, and there was no response in 8 patients (28.6%). With follow up of 10 months (range 2 to 18.5) 15 patients were in CR 53,6%, 8 patients died, 7 of then primary no responders. Analyzed by IPI, 60% of CR in intermediate high and high was obtained. The R-CHOP combination is a feasible and safe treatment in our hospitals, and 71,4 % of response was obtained in all patients and 60% of CR in high risk group.

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Rituximab Combined to ACVBP (R-ACVBP) Supported by Pegfilgrastim as a New Inductive Treatment Followed by High-Dose Consolidative Autotransplantation (HDC) for Poor Risk Diffuse Large B-Cell Lymphoma (DLBCL) in First-Line. Results of LNH 03–39B. A GELA Study.

Blood ◽

10.1182/blood.v110.11.3437.3437 ◽

2007 ◽

Vol 110 (11) ◽

pp. 3437-3437 ◽

Cited By ~ 1

Author(s):

Karim Belhadj ◽

Jean-Philippe Jais ◽

Pierre Feugier ◽

Christian Gisselbrecht ◽

Christian Recher ◽

...

Keyword(s):

Single Dose ◽

Response Rate ◽

Complete Response Rate ◽

B Cell Lymphoma ◽

Complete Response ◽

Free Survival ◽

Cd34 Cells ◽

Induction Regimen ◽

Grade 3

Abstract ACVBP dose-intense induction regimen followed by HDC provides a better event-free survival and overall survival (OS) as compared to a conventional consolidative treatment in responding patients (pts) with aggressive lymphoma presenting with 2 or 3 factors of the age-adjusted International Prognostic Index (aa-IPI). However, complete response rate (CRR = CR+CRu) after ACVBP is not superior to 65%. Besides, it is established that Rituximab (R) combined with CHOP improves CRR and OS. Several controlled studies have demonstrated that a single dose of pegfilgrastim provides similar neutrophil recovery than filgrastim after chemotherapy in cancer patients. The main objective of this study was to evaluate the efficacy of a single dose of pegfilgrastim (6 mg) at d3 of the 4 cycles of R-ACVBP inductive regimen (rituximab 375 mg/m2 d1,doxorubicin 75 mg/m2 d1, cyclophosphamide 1,200 mg/m2 d1, vindesine 2 mg/m2, bleomycin 10 mg d1 and d5 and prednisone 60 mg/m2 d1-d5) delivered every 15 days in order to maintain an optimal combined dose intensity (CDI). CDI was defined as the minimum received dose intensities of doxorubicin and cyclophosphamide by each patient. Secondary objectives were to investigate if R combined to ACVBP translates into an improvement of CRR and progression free survival (PFS). The number of leukaphereses and CD34+ cells collected in responding pts were also analyzed. Responding pts received HDC with BEAM followed by stem cell rescue. From 01/2004 to 12/2005, 60 pts were enrolled: median age was 50 y (range: 21–60), 80% with aaIPI 2 and 20% with aa-IPI 3. The mean CDI was 89 (95% CI: 86–93), greater than theoretical cut-off of 85% (p=0.0017). After induction, 63% of pts achieved CR/CRu, 25% were in PR; 2 pts died during the induction phase. At least one episode of grade 3–4 neutropenia was observed in 98% of pts, 67% experienced grade 3–4 anemia, 38% thrombocytopenia and 73% febrile neutropenia. More than 2.106 CD34+ cells/kg were collected in 80% of the pts after the 3rd and/or 4th R-ACVBP while a collection failure was observed in 11 pts (20%), 7 of them being further collected with filgrastim. The median number of leukaphereses was 2. Among the 56 responding pts, 48 received HDC. With a median follow-up of 2 years, 2-year PFS was 71% (95% CI:61–84), and OS was 91% (95% CI:74–97). We conclude that CDI is satisfactory with pegfilgrastim support. R-ACVBP dose-intense induction regimen is feasible and safe on such high-risk pts but does not increase the complete response rate. However, PFS and OS seem encouraging; a longer follow-up is needed to see whether the addition of rituximab definitely contributes to decrease the relapse rate.

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Rituximab and Reduced Dose CHOP (R-mini-CHOP) for Patients Over 80 Years with Diffuse Large B-Cell Lymphoma (DLBCL) – Groupe d'Etude Des Lymphomes De l'Adulte (GELA) Study LNH03-7B

Blood ◽

10.1182/blood.v116.21.853.853 ◽

2010 ◽

Vol 116 (21) ◽

pp. 853-853 ◽

Cited By ~ 1

Author(s):

Frederic Peyrade ◽

Fabrice Jardin ◽

Christian Gisselbrecht ◽

Antoine Thyss ◽

Jean François Emile ◽

...

Keyword(s):

Overall Survival ◽

Response Rate ◽

Performance Status ◽

Univariate Analysis ◽

B Cell Lymphoma ◽

Complete Response ◽

Albumin Level ◽

Old Patients ◽

Free Survival ◽

Grade 3

Abstract Abstract 853 Introduction: Half of the cases of DLBCL occurs in patients over 65 years but very few data are available for patients over 80 years. These older patients however seem to respond as younger patients when treatment can be tolerated. In the aim to evaluate tolerance and efficacy of a reduced dosage chemotherapy regimen associated with rituximab in this population, the GELA initiated in 2005 a prospective, multicenter, phase II study. Patients and methods: Patients older than 80 years with untreated CD20+ DLBCL, Ann Arbor stage I with bulky mass to IV and a performance status (PS) of 0 to 2 were eligible. Patients were treated with mini-CHOP chemotherapy (cyclophosphamide: 400 mg/m2 D1; doxorubicine: 25 mg/m2 D1; vincristine: 1 mg total dose D1 and prednisolone 40 mg/m2 by oral route from D1 to D5) plus rituximab (375 mg/m2 D1) every 21 days for 6 cycles. GCSF was optional. The primary objective was to evaluate the efficacy of R-mini-CHOP as measured by the overall survival. Secondary endpoints were response rate, progression free survival (PFS), event-free survival (EFS), disease-free survival (DFS) for complete responders and toxicities. Survival results are presented on an intend-to-treat basis. Response to treatment was evaluated according to 1999 Cheson criteria. Results: One-hundred-and-fifty-patients (51 male, 99 female) were included in 38 centers of the GELA. The median age was 84 years (range 80–95). Seventy-five percent of patients had a stage III/IV. LDH level was elevated in 69% of patients. Age-adjusted (aa) IPI was 2–3 in 66% of patients. One-hundred-twenty-nine patients completed the first three cycles and 108 received the whole regimen. The Dose-Intensity for patients who completed the three first cycle was 100% and 96.8% for doxorubicine and cyclophosphamide respectively. Thirty-six percent of patient received at least one injection of GCSF. The overall response rate was 74%, including 40% of complete response and 23% of unconfirmed complete response. At the time of this analysis, in July 2010, the median follow-up time was 20 months. The 2-year overall survival was 58.9% [95% CI: 49.3–67.2%]. The two-year estimated PFS, EFS and DFS were 47.4% [95% CI: 38.1–56.2%], 44.8% [95% CI : 35.7–53.6%] and 56.6% [95% CI : 49.3–67.2%] respectively. Hematological toxicity was the most common side effect. Grade 3–4 neutropenia was observed in 39% of the patients and grade 3–4 thrombocytopenia in 7%. Eleven patients (7%) experienced at least one episode of febrile neutropenia. Overall patients experienced a median of 4 nights of hospitalization during treatment phase (range 0–46). Thirty patients died during the treatment evenly distributed between treatment toxicity (6.7%) lymphoma (6.7%) and intercurrent causes (6.7%). In a univariate analysis, PS 0 or 1, aaIPI 0 or 1, number of extra-nodal sites <2, albumin level >35g/l, mass <10cm and a high IADL (Instrumental activities of daily living) score appear to be highly predictive of a prolonged survival. In a multivariate analysis a PS equal to 0 or 1 and an albumin level >35 g/l were significantly associated with a longer survival. Conclusion: In patients over 80 years with DLBCL and a good performance status, immunochemotherapy with R-mini-CHOP appears to be safe and effective, indicating that a substantial proportion of very old patients could indeed be cured. This regimen could be considered as a platform for the introduction of new drugs in the first line treatment of this population. Disclosures: No relevant conflicts of interest to declare.

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Evaluation of R-CHOP and R-CVP in the treatment of elderly patient with non-Hodgkin lymphoma

MedPharmRes ◽

10.32895/ump.mpr.3.3.1 ◽

2019 ◽

Vol 3 (3) ◽

pp. 1-6

Author(s):

Truc Phan ◽

Tram Huynh ◽

Tuan Q. Tran ◽

Dung Co ◽

Khoi M. Tran

Keyword(s):

Elderly Patients ◽

Hodgkin Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

The Elderly ◽

Free Survival ◽

Non Hodgkin Lymphoma ◽

Common Sign ◽

Related Mortality

Introduction: Little information is available on the outcomes of R-CHOP (rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone) and R-CVP (rituximab with cyclophosphamide, vincristine and prednisone) in treatment of the elderly patients with non-Hodgkin lymphoma (NHL), especially in Vietnam. Material and methods: All patients were newly diagnosed with CD20-positive non-Hodgkin lymphoma (NHL) at Blood Transfusion and Hematology Hospital, Ho Chi Minh city (BTH) between 01/2013 and 01/2018 who were age 60 years or older at diagnosis. A retrospective analysis of these patients was perfomed. Results: Twenty-one Vietnamese patients (6 males and 15 females) were identified and the median age was 68.9 (range 60-80). Most of patients have comorbidities and intermediate-risk. The most common sign was lymphadenopathy (over 95%). The proportion of diffuse large B cell lymphoma (DLBCL) was highest (71%). The percentage of patients reaching complete response (CR) after six cycle of chemotherapy was 76.2%. The median follow-up was 26 months, event-free survival (EFS) was 60% and overall survival (OS) was 75%. Adverse effects of rituximab were unremarkable, treatment-related mortality accounted for less than 10%. There was no difference in drug toxicity between two regimens. Conclusions: R-CHOP, R-CVP yielded a good result and acceptable toxicity in treatment of elderly patients with non-Hodgkin lymphoma. In patients with known cardiac history, omission of anthracyclines is reasonable and R-CVP provides a competitive complete response rate.

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Feasibility study of TAS-118 plus oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.205 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 205-205

Author(s):

Daisuke Takahari ◽

Manabu Ohashi ◽

Atsuo Takashima ◽

Takuro Mizukami ◽

Naoki Ishizuka ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Locally Advanced ◽

Dose Intensity ◽

Complete Response ◽

Free Survival ◽

D2 Gastrectomy ◽

Locally Advanced Gastric Cancer ◽

Grade 3

205 Background:TAS-118 (S-1 and leucovorin) + oxaliplatin (L-OHP) improved overall survival (OS) compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC) (Kang, Lancet Oncol. 2020). This study investigated the feasibility of peri (pre and post)-operative (op) chemotherapy (chemo) with TAS-118 ± L-OHP in pts with locally advanced resectable GC. While it was reported that pre-op TAS-118 + L-OHP followed by D2 gastrectomy was well tolerated and showed promising efficay (Takahari, ASCO-GI. 2020), the recommended post-op chemo regimen, TAS-118 or TAS-118 + L-OHP, has yet to be determined. Methods:Eligible pts with GC of clinical T3-4N1-3M0 were enrolled. The protocol treatment consisted of pre-op chemo with 4 courses of TAS-118 (40-60 mg/body, orally, twice daily, 7 days) + L-OHP (85 mg/m2, intravenously, day 1) in a 2-week cycle, and gastrectomy with D2 lymphadenectomy, followed by post-op chemo with 12 courses of TAS-118 (step 1) and 8 courses of TAS-118 + L-OHP (step 2). Step 2 was started if the dose-limiting toxicity (DLT) occurred in < 6 of 10 pts in step 1. Up to 20 pts were included in the analysis of feasibility after a recommended regimen was determined. Results:Between December 2016 and February 2019, 45 pts were enrolled. The numbers of pts with cT3/4a and cN1/2/3 were 13/32 and 25/17/3, respectively. Excluding 14 pts (4 achieving pathological complete response, 4 not satisfying the criteria for post-op chemo, 3 physician judgement or pt withdrawal, 2 progressive disease, 1 adverse event [AE]), 31 pts (11/20 in step 1/2) received the post-op chemo. No DLT was observed in either step. The post-op chemo completion rate was 90.9% (95% CI, 63.6-99.5) in step 1 and 80.0% (95% CI, 59.9-92.9) in step 2. The median relative dose intensity of TAS-118 in step 1 was 83.3%, and those of TAS-118 and L-OHP in step 2 were 69.9% and 74.3%, respectively. One pt in step 2 discontinued post-op chemo due to AE. Grade ³ 3 AEs observed in ≥ 10% of pts were weight loss in both step 1 and step 2 (2 in each), and hypokalemia (n = 3) and neutropenia (n = 2) in step 2. At 1-year follow-up after the last pt was enrolled, recurrence-free survival and OS rates were 91.1% (95% CI, 78.0-96.6) and 100%, respectively at 12 months, and 69.1% (95% CI, 49.6-82.3) and 95.5% (95% CI, 71.9-99.3), respectively at 24 months. Conclusions:Taken together with the feasibility and efficacy of pre-op chemo, peri-op chemo with TAS-118 + L-OHP with D2 gastrectomy was well tolerated and showed promising efficacy. Clinical trial information: UMIN000024688.

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Abstract 16154: Baseline Left Ventricular Diameter Predicts Recovery in New Systolic Heart Failure Syndromes

Circulation ◽

10.1161/circ.142.suppl_3.16154 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Daniel Gold ◽

Nathan Kong ◽

Matthew Gold ◽

Tess Allan ◽

Anand Shah ◽

...

Keyword(s):

Left Ventricular ◽

Medical Decision ◽

Left Ventricular Ejection ◽

Internal Diameter ◽

Event Free Survival ◽

Short Term Treatment ◽

Ventricular Ejection Fraction ◽

Free Survival ◽

Advanced Therapies

Introduction: It is unknown how often patients with very advanced left ventricular (LV) dilation at initial presentation demonstrate meaningful recovery with medical therapy. Understanding short term treatment outcomes may impact medical decision making and counseling. Hypothesis: Patients with left ventricular end diastolic internal diameter (LVEDD) > 6.5cm will be less likely to recover left ventricular ejection fraction (LVEF) as compared to patients with LVEDD < 6.5cm. Methods: Patients were retrospectively identified by a database search of echocardiogram studies obtained at the University of Chicago between 2008-2018. Manual review was performed to ensure new diagnosis of systolic dysfunction with LVEF ≤ 35% and follow up echocardiogram study within 3 to 9 months of index study. LVEDD was determined from parasternal long axis views per routine. LVEF recovery was specified as LVEF > 35%. Chart review was done to assess for composite death, hospice, transplant, left ventricular assist device, and sustained ventricular tachycardia. Chi-square, multivariable logistic regression, and Kaplan-Meier survival were used for analysis. Results: Out of 100 patients included for analysis, mean age was 59.7 years, 41 were female and 82 were African American. 17.7% of patients’ with LVEDD > 6.5 cm had LVEF recovery compared to 53.0% of patients’ with LVEDD ≤ 6.5 cm (p = 0.008). LVEDD > 6.5 cm was associated with less LVEF recovery even when adjusted for age, gender, hypertension, and diabetes (adjusted odds ratio 0.18, 95% CI 0.04 to 0.65). LVEDD > 6.5cm was associated with worse event free survival (p = 0.004) with a median follow-up time of 2.4 years. Conclusions: An LVEDD of > 6.5cm is associated with diminished LVEF recovery and event free survival when compared to those patients with an LVEDD ≤ 6.5cm. Delaying consideration for advanced therapies and device based therapies in hopes of recovery may be inappropriate for many such patients.

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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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Bendamustine and Rituximab: Complete Response in a 62-Year-Old Female with an Aggressive Lymphoma and an Ejection Fraction of 20%

Chemotherapy ◽

10.1159/000452756 ◽

2016 ◽

Vol 62 (2) ◽

pp. 140-146

Author(s):

Taha Alrifai ◽

Kelly Grant Szymanski ◽

Parameswaran Venugopal ◽

Brett Mahon ◽

Tochukwu Okwuosa ◽

...

Keyword(s):

Ejection Fraction ◽

B Cell Lymphoma ◽

Complete Response ◽

Left Ventricular ◽

Aggressive Lymphoma ◽

Left Ventricular Ejection ◽

Ventricular Ejection Fraction ◽

Non Hodgkin Lymphoma ◽

Aggressive Subtype ◽

Standard Treatment Regimen

The treatment of diffuse large B-cell lymphoma in the presence of cardiac comorbidities can be challenging considering that the standard treatment regimen used for this aggressive subtype of non-Hodgkin lymphoma (NHL) consists of a combination of rituximab, cyclophosphamide, doxorubicin hydrochloride, Oncovin (vincristine), and prednisone (R-CHOP). The use of the anthracycline doxorubicin has been associated with arrhythmias and cardiomyopathy, making patients with cardiac dysfunction poor candidates for R-CHOP. As such, it is imperative to find alternative regimens that omit cardiac toxicity without compromising efficacy for this patient population. We report a case of composite NHL in a patient who received frontline bendamustine with rituximab with encouraging results. Our patient had a left ventricular ejection fraction of 20%, making her a poor candidate for anthracycline-based therapy. We opted to administer bendamustine with rituximab for a total of 6 cycles. She remains disease free 18 months after the completion of therapy.

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