Real-World Conditional Survival Analysis of Patients with Relapsed/Refractory Classical Hodgkin's Lymphoma in the US

Introduction:While the majority of patients (pts) with newly diagnosed classical Hodgkin's lymphoma (cHL) achieve remission following first-line therapy, approximately 30-40% will relapse or become refractory (R/R). Despite R/R status, the 5-year relative survival rate in this population is high (ranging from 78% to 92%) (American Cancer Society 2020). While overall survival (OS) is an unambiguous measure of efficacy in clinical trials, using it as a primary end point requires a long duration of follow-up and may prolong the process of identifying novel and potentially beneficial therapy. Surrogate outcomes, such as progression-free survival (PFS) and time to progression (TTP) are sometimes regarded as valid alternatives when assessing efficacy of a treatment in the absence of mature OS data. The objectives of this study were to assess the conditional survival (CS) given prior PFS among R/R cHL pts treated in the real-world setting. Methods:This retrospective cohort study used electronic medical record (EMR) data of US pts from a network of oncology practices, including practices affiliated with CancerLinQ, maintained in the Definitive Oncology Dataset. Eligible adult (≥18 years) pts who had a confirmed diagnosis of cHL and ≥1 R/R event that occurred between 2000 to 2019 were included. Refractory disease was defined as not achieving a complete or partial response (CR or PR) during a line of therapy. Relapsed disease was defined as the reappearance of cHL at any time after the end of treatment after having achieved a CR or PR. PFS and OS were measured from the start of second-line [2L] therapy to the earlier or disease progression or death; pts without evidence of disease progression or death were censored at the last observed visit. The association between PFS and OS was quantified through the nonparametric Kendall tau rank correlation for bivariate censored data. CS was defined as the Kaplan-Meier probability of surviving an additionalymonths (from the start of 2L), given no OS or PFS event in the previousx(< y) months. Results:A total of 286 R/R cHL pts were included. Most pts were Caucasian (77.3%, n=221) with a median age of 35 years (range: 19-86) at the first R/R event. Median length of follow-up was 12 months from the first R/R event. The most common B symptoms reported were night sweats (38.8%, n=111), weight loss (36.4%, n=104), and fatigue (27.3%, n=78). More than half of pts (54.9%, n=157) received autologous stem-cell transplant (SCT) and 6.6% (n=19) received allogenic SCT. Two-hundred twenty-six pts (79.0%) had documented 2L therapy (first R/R event). From the first R/R event, among these 226 pts, median PFS was 21.0 months (95% confidence interval [CI]: 15.1, 52.5) and median OS was 146.7 months (95% CI: 119.9, not achieved [NA]). CS rates among pts alive without disease progression increased with time: 1-year and 6-year survival rates were 95.7% (95% CI: 91.5, 97.8) and 79.3% (95% CI: 70.5, 85.7), respectively, in pts alive without progression at 3 months, but increased to 100.0% (95% CI: 100, 100) and 94.6% (95% CI: 79.9, 98.6) in pts alive without progression at 3-years (Table). The calculated Kendall tau correlation was 0.42 (p<0.0001), which suggested a statistically significant dependence between PFS and OS. Conclusion:In the real-world setting, R/R cHL pts with longer time without disease progression had lower rates of death and better prognosis. Results from this study support a relationship between PFS and OS; however, further validation and acceptance of PFS as a surrogate endpoint in cHL is required. Establishing these relationships may inform future clinical trial design and interpretation of interim trial data. Disclosures Desai: Merck & Co., Inc:Current Employment, Current equity holder in publicly-traded company.Yang:Merck & Co, Inc.:Current Employment.Gilligan:ConcertAI:Current Employment;Merck & Co., Inc.:Research Funding.Li:Merck & Co., Inc.:Current Employment, Current equity holder in publicly-traded company.Raut:Merck & Co., Inc.:Current Employment.Nahar:Merck Sharp & Dohme, Corp., a subsididary of Merck & Co., Inc., Kenlworth, NJ, USA:Current Employment.

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Treatment patterns among patients with higher-risk myelodysplastic syndromes in a real-world setting: Electronic medical record (EMR)-based data.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.8_suppl.247 ◽

2017 ◽

Vol 35 (8_suppl) ◽

pp. 247-247

Author(s):

Bruce Jeffrey Dezube ◽

Jill Bell ◽

Aaron Galaznik ◽

Eileen Farrelly ◽

Marlo Blazer ◽

...

Keyword(s):

Real World ◽

Index Date ◽

Treatment Guidelines ◽

Specific Treatment ◽

Cell Transplant ◽

Newly Diagnosed ◽

Limited Information ◽

Nccn Guidelines ◽

Real World Setting

247 Background: Treatment decisions in MDS are based on a prognostic scoring system that divides pts into five distinct risk categories (NCCN 2016). Treatment guidelines for HR MDS pts include hypomethylating agents (HMAs) alone (azacitidine & decitabine), high-intensity induction chemotherapy (IC), & stem cell transplant (SCT) alone or after HMAs. Limited information is available on how these recommendations are applied in practice. This study evaluated the real-world treatment of HR MDS pts. Methods: Newly diagnosed HR MDS pts who were ≥18 years old & initiated first-line therapy (1LT) were retrospectively identified from a large United States EMR database between 1/1/2008 & 7/31/2015. As complete cytogenetics were not available in the database, HR was based on: ICD coding: ≥1 inpatient claim with an HR MDS ICD-9/10 code (ICD-9 code: 238.73; ICD-10 codes: D46.20, D46.21, D46.22), or ≥2 outpatient claims with an MDS ICD-9/10 code, or an adapted HR MDS algorithm (NCCN Guidelines in Oncology for MDS v.1.2016; Greenberg, et al. Blood. 2012;120:2454-65; Schanz et al. J Clin Oncol. 2012;30:820-9). The first MDS claim served as the index date. 1LT was defined as an MDS-specific treatment initiated on or after the index date. Pts were followed until death, progression to acute myeloid leukemia (AML), loss to follow-up, or end of study (9/30/2015). Results: 720 newly diagnosed HR MDS pts were identified; of these, 229 (32%) pts received MDS-specific treatment. Median time to treatment was 22 days (interquartile range [IQR]: 10, 74). HMAs were the most common agents in the 1LT with 60% (n= 138) & 24% (n=54) receiving azacitidine & decitabine, respectively. Lenalidomide was used in 7.4% of pts (n=17), 4.8% received SCT alone (n=11), & 3.9% (n=9) received IC. At median follow-up of 9.4 months (IQR: 4.3, 18.4), 38% (n=86) died & 28% (n=63) progressed to AML. Conclusions: Despite guidelines, most HR MDS pts in a real-world setting were not treated with MDS-specific treatment. Among treated pts, 1LT with HMAs & azacitidine predominated. Subsequent research is needed to understand reasons for lack of treatment.

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A Single Center Review Evaluating Daratumumab Outcomes in Multiple Myeloma Patients at Monter Cancer Center/Northwell Health Cancer Institute

Blood ◽

10.1182/blood-2020-143203 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 25-25

Author(s):

Chung H Chen ◽

Chung-Shien Lee ◽

Samrah Ahmad ◽

Monique Hartley-Brown

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

Disease Progression ◽

Real World ◽

Time Frame ◽

Cancer Center ◽

Published Data ◽

The Real ◽

Risk Of Death ◽

Real World Setting

Multiple myeloma (MM) is a malignant neoplasm of plasma cells in bone marrow. Daratumumab (Dara) is a CD38-directed antibody which is Food and Drug Administration (FDA) approved for treatment of patients with MM. Dara is recommended by the National Comprehensive Cancer Network (NCCN) guidelines, which many community oncologist use as the standard of care guidelines. Therefore, we consider it important to analyze Dara use and effects in the real-world community Oncology clinic setting. We evaluated the survival outcomes, both progression-free survival (PFS) and overall survival (OS), as well as the time to progression (TTP) of MM and common adverse events (ADEs) seen in patients at a single site, Monter Cancer Center in the Northwell Health (NH) system. This is a single group study evaluating outcomes of patients with MM who received Dara at NH. Primary objectives include evaluating OS, defined as time from initiating Dara therapy to time of death from any cause. Secondary objectives include PFS, time from initiation of Dara therapy to documented disease progression. We also plan to evaluate time to next treatment (TTNT), TTP and rate of ADEs within 30 days of initiating Dara. This is a retrospective study of patients with MM who received Dara at Monter Cancer Center, Northwell Health Cancer Institute. Basic demographics; gender, age at diagnosis, body mass index (BMI), and ethnicity, were collected. Treatment information collected included, previous number of therapies, dose of Dara in total and per body weight in kg, number of doses of Dara received. Data was collected using electronic medical records from January 2015 through December 2019. Patient charts were reviewed, collecting data from the time of diagnosis and initiation of Dara to date of last known follow-up, or death. Progression of disease information and initiation of new therapy was collected during this time frame. Standard methods of survival analysis were used to analyze the primary objectives. Kaplan-Meier estimate was used to analyze PFS and OS at 6, 12, 24, and 36 months. TTNT was defined as length of time from the date of initiation of Dara to the date the patient was started on a new therapeutic regimen. TTP was defined as the date the patient started Dara therapy to the date of documentation of disease progression or relapse. Cumulative incidence rates were calculated to determine the rates of incidence of next treatment in the presence of competing risk of death, and rate of ADEs in patients during this time frame. Rate of ADEs were reported with corresponding 95% confidence intervals using a binomial confidence interval. A total of 50 patients were included in the analysis. Baseline demographics are in line with published data, mean age was 68.8 years, with a non-Caucasian predominance of 68% to 32% Caucasian. The gender profile was 42% male. Prior mean number of therapies was 2.9, with a median of 2. Dose of Dara used was in line with the recommended dosing with mean 16.3mg/kg dosing. The mean number of doses received were 17. Similar to prior published data the predominant heavy chain MM phenotype was IgG at 48%. The OS, at 36 months was 54%, where 23 patients (46%) had documented date of death during the 5-year time span reviewed. Thirty-one patients (62%) experienced disease progression (TTP), ranging from 28 to 1047 days from start of Dara treatment, with a median TTP of 317 days. The median PFS was 436 days (95% CI: 334-676 days). There were 46% patients that continued on another line of therapy post Dara , with the TTNT ranging from 25 to 541 days, median 175 days from initial Dara therapy. Among patients who had at least one adverse event, the most frequently occurring pattern was fatigue, pyrexia, and chills at 22%, followed by infusion related reactions at 20%. Dara has shown strong clinical efficacy clinical trials. The patients in clinical trials are often not reflective of real-world clinical patients. This study evaluates patients at a single cancer center in the NH system. The data reinforces the efficacy and tolerability of Dara in the real-world setting. It also depicts the difference in OS, PFS, TTP, TTNT and ADEs in the real-world setting. The data suggests Dara outcomes in community-based oncology centers vary from clinical trial data. However, it does indicate similar improved benefits in OS, PFS and TTNT compared with other retrospective studies at other centers. Further prospective studies would be beneficial in evaluating this real-world impact. Disclosures No relevant conflicts of interest to declare.

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Real-World Study of CPX-351 Treatment Outcomes for Acute Myeloid Leukemia (AML) in England

Blood ◽

10.1182/blood-2021-148450 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2310-2310

Author(s):

Alex Legg ◽

Pesheya Doubleday ◽

Adam Reich ◽

Alexandrina Lambova ◽

Greg Medalla

Keyword(s):

Real World ◽

Salvage Therapy ◽

Group Performance ◽

De Novo ◽

Cell Transplant ◽

Publicly Traded ◽

Probability Of Survival ◽

De Novo Aml ◽

The Impact

Abstract Introduction: CPX-351 (US: Vyxeos ®; Europe: Vyxeos ® Liposomal) is a dual-drug liposomal encapsulation of daunorubicin and cytarabine in a synergistic 1:5 molar ratio. Since November 2018, the National Institute for Health and Care Excellence (NICE) has recommended its use for adults with newly diagnosed, therapy-related AML (t-AML) or AML with myelodysplasia-related changes (AML-MRC) due to either prior myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) or de novo AML with myelodysplasia-related cytogenetic changes. The key aims of this study were to utilize the Cancer Analysis System (CAS) database available through the National Cancer Registration and Analysis Service (NCRAS) to describe the demographics and clinical characteristics of adults with AML in England who have received CPX-351, as well as to estimate overall survival (OS) and survival within stratifications of interest. Methods: The NCRAS systematically collects and curates population-level data about cancer diagnoses, treatments, and outcomes across England. Adults (aged ≥18 years) diagnosed with AML and treated with CPX-351 were included in this study. A diagnosis of t-AML or AML-MRC between January 2013 and March 2020 was determined either directly using International Classification of Diseases for Oncology, Third Edition (ICD-O-3) codes or indirectly using non-specific ICD-O-2, ICD-O-3, or ICD-10 AML codes in combination with either prior systemic anticancer therapy or radiotherapy (t-AML) or a prior diagnosis of MDS or CMML (AML-MRC; other AML-MRC subtypes could not be specifically identified and are included within the de novo AML subgroup). OS was measured from the date of diagnosis; a separate analysis of OS landmarked from the date of hematopoietic cell transplant (HCT) was also performed. Within this preliminary analysis, no OS adjustments have been made to account for any COVID-19-related deaths. Results: A total of 172 patients with AML who were treated with CPX-351 were identified: 37 (22%) had t-AML, 57 (33%) had AML-MRC, and 78 (45%) had de novo AML. At diagnosis, the mean (standard deviation) age was 62.8 years (10.1), with 49/172 (28%) patients aged <60 years; 66% of patients were male; 87% were white; and most had an Eastern Cooperative Oncology Group performance status of 0 or 1 (68%). Six (3%) patients had received azacitidine treatment for a prior malignancy. To date, 43/172 (25%) patients had undergone HCT overall, including 43/97 (44%) patients with ≥3 months of follow-up. The cut-off date for OS was December 31, 2020, giving a median (interquartile range) follow-up of 11.2 months (3.6, 16.9). Overall, 91 patients had died, with an estimated median OS (95% confidence interval [CI]) of 16.6 months (11.0, not estimable) and probability of survival (95% CI) at 1 and 2 years of 0.54 (0.47, 0.62) and 0.39 (0.30, 0.50), respectively (Figure 1). Early mortality rates were 7% at 30 days and 15% at 60 days. When OS was landmarked from the date of HCT, median OS was not reached, with a probability of survival (95% CI) at 1 year of 0.74 (0.62, 0.89; Figure 2). When stratified by age, estimated median OS (95% CI) was not reached for patients aged <60 years and 12.8 months (8.9, 17.6) for patients aged ≥60 years. In a treatment patterns analysis that evaluated second-line treatments after CPX-351, 68 patients died without salvage therapy and 64 were alive without receiving subsequent therapy by the end of the study period. The most common salvage treatments were fludarabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor (FLAG-Ida; n = 15), daunorubicin plus cytarabine (DA)-based therapy (n = 6), and azacitidine alone (n = 7). Of the 43 patients who received an HCT, 6 (14%) underwent HCT following salvage therapy. Conclusions: This is the largest study to date examining the real-world outcomes for patients with AML who were treated with CPX-351. The estimated median OS of 16.6 months is consistent with reported real-world outcomes for CPX-351 in French and Italian studies. Median OS has not been reached in patients aged <60 years or when landmarked from the date of HCT. Once the CAS database has been updated, these analyses will be repeated to increase follow-up and patient numbers and to determine the impact of COVID-19 on OS following CPX-351 treatment. Figure 1 Figure 1. Disclosures Legg: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company. Doubleday: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Reich: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Lambova: IQVIA Inc., which was contracted by Jazz Pharmaceuticals for the conduct of this analysis: Current Employment. Medalla: Jazz Pharmaceuticals: Current Employment, Current equity holder in publicly-traded company.

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Adalimumab for the treatment of refractory active and inactive non-infectious uveitis

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2017-311234 ◽

2018 ◽

Vol 102 (12) ◽

pp. 1672-1678 ◽

Cited By ~ 10

Author(s):

Jonathan TL Lee ◽

William B Yates ◽

Sophie Rogers ◽

Denis Wakefield ◽

Peter McCluskey ◽

...

Keyword(s):

Treatment Failure ◽

Real World ◽

Treatment Success ◽

Immunosuppressive Agents ◽

Vascular Lesions ◽

The Real ◽

Real World Setting ◽

Long Term Treatment ◽

Infectious Uveitis

Background/aimsTo compare the efficacy of adalimumab in eyes with active and inactive non-infectious uveitis in the real-world setting.MethodsMulticentre, retrospective, chart review of patients with refractory non-infectious uveitis treated with adalimumab. Main outcome measures included reduction of prednisolone dose, ability to taper immunosuppressives and a composite endpoint of treatment failure encompassing active inflammatory chorioretinal or retinal vascular lesions, intraocular inflammation grade and visual acuity.ResultsThirty-seven eyes of 22 patients were studied. Mean follow-up was 20.1 months (median: 13). Most had either posterior or panuveitis (n=12, 55%). Mean duration of uveitis at baseline was 83.2 months (median: 61), where the majority (n=15, 68%) had already been treated with two or more conventional immunosuppressive agents in addition to prednisolone. Oral prednisolone was reduced to ≤10 mg/day in 9 of 12 patients (75%) by 6 weeks. At 6 months of therapy, nine (90%) of the active eyes achieved a 2-step improvement in anterior chamber inflammation, with six (60%) demonstrating a similar improvement in vitreous haze grade. Almost all (n=17, 94%) of the initially inactive eyes maintained clinical quiescence at this time point. The incidence rate of treatment failure during follow-up was 88 per 100 eye-years for the active eyes and 24 per 100 eye-years for the initially inactive eyes. There were no serious adverse effects.ConclusionAdalimumab appears to reduce the corticosteroid burden in active and inactive non-infectious uveitis in the real-world setting. Inflammatory activity at the time of adalimumab commencement may determine long-term treatment success.

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Treatment Outcomes and Toxicity Profile of Kyprolis in Multiple Myeloma: A Single Institution Experience

Blood ◽

10.1182/blood-2020-143173 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 1-2

Author(s):

Richa Thakur ◽

Nina Kohn ◽

Monique Hartley-Brown

Keyword(s):

Multiple Myeloma ◽

Clinical Trials ◽

High Risk ◽

Disease Progression ◽

Real World ◽

Cell Transplant ◽

Single Center ◽

The Real ◽

Overall Response ◽

Increased Risk

Background: Survival outcomes of Multiple Myeloma (MM) patients have significantly increased with recent advances in treatment. In the past decade several agents have been FDA approved due to improvement in the progression-free survival (PFS). Kyprolis is an irreversible proteasome inhibitor (PI) that was first approved in 2012 for treatment of MM. The real-world use of Kyprolis in treatment of MM is important to assess. Aim: The primary objective of this study is to evaluate the real-world outcome in overall response rates (ORR) for MM patients treated with Kyprolis. This was a retrospective study at a single center site in the Northwell Health system, evaluating patients at the Monter Cancer Center. Secondary objectives include determining the PFS, and adverse side effects (ADEs), including cardiovascular and renal toxicities of MM patients treated with Kyprolis at our institution. Methods: We retrospectively analyzed the charts of patients with a known diagnosis of MM who were treated with Kyprolis between January 1, 2013, and December 31, 2018. Baseline patient demographics such as age, gender, MM stage at diagnosis based on the Revised International Staging System (R-ISS) criteria, cytogenetics and fluorescence in situ hybridization (FISH), prior treatment regimens, autologous stem cell transplant (ASCT) were collected. Statistical methods included percentage calculations of baseline characteristics. Time to progression was measured from start of treatment to disease progression. PFS was calculated as a mean from initiation of treatment to the time point when progression was first noticed. Results: We identified 66 patients who fit our criteria of inclusion in this study. The median age was 65 years (Range 48 to 84). Based on the R-ISS staging, 7 (10%) patients were stage I, 28 (42.4%) stage II, and 31 (47.0%) were stage III. Based on cytogenetics 31% of the patients were classified as high risk (defined as having a 13q deletion, t (4,14), del(17p), t (14,16), or gain 1q). There were 32.3% of the patients with hyperploidy. A subset of patients was heavily pretreated with approximately 18.2% receiving more than 4 treatment lines prior to initiation of Kyprolis and 22.7% having received 3 prior lines. 42.4% of patients received 2 prior lines of MM- directed therapy. Prior treatments mainly included immunomodulatory agents (IMiDs) such as Lenalidomide and Proteosome Inhibitors (PIs) such as Bortezomib. Cyclophosphamide in combination with Bortezomib and dexamethasone (CyBorD) was also a frequent pre-treatment regimen. In regards to ASCT, 42.4% of patients had undergone prior ASCT before Kyprolis therapy. The overall response rate was 77.2%, with 6.2% having obtained a complete response (CR) as defined by the International Myeloma Working Group response criteria. Thirty-five (53%) patients terminated Kyprolis due to disease progression or intolerance and underwent a change in their treatment. There were 10 patients (15%) who required ASCT after receiving Kyprolis in the setting of progression of disease. The majority of patients that progressed received Daratumumab (40%) or Pomalidomide (46%). Regarding ADEs, grade 2 hypertension was noted in 14% of all patients, acute renal failure (ARF) in 17% of patients, dyspnea in 25.4%, gastrointestinal (GI) toxicity in 16.3%, and fatigue in 40.8% of patients who received Kyprolis. The median PFS on Kyprolis at this site was 6.96 months. Conclusion: Our study shows that Kyprolis improved PFS in patients with MM. However, these patients are at increased risk for cardiac and renal toxicity. This study varies from published findings of clinical trials. Our patients had a higher percentage of high-risk cytogenetics as compared to those in the ASPIRE trial. About 90% of patients in the ASPIRE study had an ECOG status of 0 or 1, which was better than the average seen in our patient population. These two factors may have contributed to a lower observed PFS than that initially observed in the clinical trials. Second, this is a retrospective single center study, with inherent biases that may result in additional variance. The proportion of grade 2 ADEs were comparable to the frequencies reported in the ASPIRE and ENDEAVOR trials. The toxicities noted in this study reinforce the importance for community oncologists to be aware of these issues. Early prevention and management may impact quality of life, response, or tolerance to Kyprolis therapy. Disclosures No relevant conflicts of interest to declare.

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Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Relapsed/Resistant Hodgkin’s Lymphoma.

Blood ◽

10.1182/blood.v104.11.5135.5135 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5135-5135

Author(s):

Michele Carella ◽

Germana Beltrami ◽

Maria T. Corsetti ◽

Mario M. Greco ◽

Potito Scalzulli ◽

...

Keyword(s):

Hodgkin’S Lymphoma ◽

Progressive Disease ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Hodgkin's Lymphoma ◽

Mixed Chimerism ◽

Maximal Response ◽

High Dose ◽

Cell Transplant

Abstract Background: We postulated that it is possibile to safely extend the benefit of allografting to relapsed or resistant Hodgkin’s Lymphoma (HL) by combining cytoreduction with high-dose therapy/autologous stem cell transplant (HDT/ASCT) and graft versus HL effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT). Methods: Twenty-two patients, 32 years of age (range, 16–39) with heavily pretreated disease were given HDT/ASCT. At a median of 92 days after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and non-T depleted donor peripheral blood stem cells from HLA-identical siblings. Postgrafting immunosuppression consisted of methotrexate and cyclosporine. Cyclosporine was withdrawn early in patients with mixed chimerism or disease progression. Donor lymphocyte infusions were given to 12 patients with stable mixed chimerism and/or progressive disease. Results: Seventeen patients (77%) achieved full chimerism and 5 patients mixed chimerism. Twelve patients (55%) achieved CR after tandem transplant. The first signs of responsiveness in CR patients began at day ≥60 and the maximal response was achieved on day ≥80. The remitters patients achieved full chimerism and developed acute/chronic GVHD before regression of the disease; moreover, 5 patients achieved CR after DLI. At last follow-up (July 31, 2004), 9 out of 12 CR patients are alive at a median of 1844 days (range, 1092 to 2045). Subsequently, 5 patients relapsed and are now alive on therapy and four patients maintain CR after a median follow-up of 1874 days (range, 1092–2045). Acute GVHD grade ≥ II occurred in 9 patients (40%); chronic GVHD developed in 5 patients (23%), four of them with extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of GVHD/infections, 1 patient died of extensive chronic GVHD and 7 patients of progressive disease. Conclusions: This tandem auto-allotransplant protocol demonstrated to be highly effective also in advanced resistant Hodgkin’s Lymphoma patients. The exploitation of graft-versus-lymphoma effect is a promising finding

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Atezolizumab in first-line treatment of metastatic nonsquamous non-small cell lung cancer in the real-world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21112 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21112-e21112

Author(s):

Javier De Castro ◽

Begoña Campos Balea ◽

Diego Perez Parente ◽

Letizia Polito ◽

Marcus Lawrance ◽

...

Keyword(s):

Real World ◽

Real Life ◽

Phase Iii ◽

Egfr Mutations ◽

First Line ◽

Early Adopters ◽

The Real ◽

Real World Setting ◽

Health Database

e21112 Background: The phase III IMpower150 study showed efficacy benefits with atezolizumab in combination with bevacizumab, carboplatin and paclitaxel (ABCP; arm B) as first-line (1L) treatment for patients (pts) with metastatic non-squamous (nsq) NSCLC. The FDA approved this regimen for these pts (with no EGFR or ALK mutations [WT]) on December 2018. However, to date there is limited evidence on its use in real life. This study aimed to explore the use of ABCP in the real-world setting and to describe the characteristics of early adopters (those who received ABCP in 1L). Methods: Data were extracted from the Flatiron Health database (US population). Pts with advanced stage IIIB/IV nsq NSCLC at diagnosis receiving ABCP regimen in any line were eligible for the study. Finally, early adopters were selected. Results: A total of 67 pts received the ABCP regimen in 1L. Baseline characteristics for these pts and comparisons with the IMpower150 population are summarized in Table. Real-world (rw) response in the WT group ( n = 49; 6 pts were excluded due to EGFR mutations and 12 because minimum follow-up was not reached) was similar to that of the IMpower150 series (rwRR: 55.1% [40.2-69.3] vs. 63.5% [58.2-68.5]), despite the WT population being older with a higher proportion of ECOG PS = 1. In patients who would have met the IMpower150 inclusion criteria ( n = 24), rwRR was 70.8% (48.9-87.4). Conclusions: The ABCP regimen has been adopted in the real-world setting. In terms of efficacy, response rates and current PFS data were in line with trial results, despite the population being unselected and having a worse clinical profile. Longer follow-up is required for rwOS data. vs. arm B IMpower150 results.[Table: see text]

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Brentuximab vedotin with chemotherapy for advanced stage untreated classic Hodgkin’s lymphoma in a real-world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e20020 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e20020-e20020

Author(s):

Raphael Steiner ◽

Frederick M Cramer ◽

Prachee Singh ◽

Melody Becnel ◽

Pedro E Alcedo ◽

...

Keyword(s):

Real World ◽

Hodgkin’S Lymphoma ◽

Standard Dose ◽

Brentuximab Vedotin ◽

Hodgkin's Lymphoma ◽

Phase Iii ◽

Advanced Stage ◽

Pivotal Phase ◽

Real World Setting ◽

Grade 3

e20020 Background: In the pivotal phase III study ECHELON-1, Brentuximab Vedotin (BV), doxorubicin, vinblastine, and dacarbazine (A+AVD) demonstrated superior efficacy but more hematological and neurological toxicity than bleomycin+AVD (ABVD) as therapy of advanced-stage untreated classic Hodgkin’s lymphoma (ucHL) (Straus et al Blood 2020). It is unknown if A+AVD in a real world setting shows the same efficacy and safety profile. Methods: After obtaining institutional research approval, we retrospectively reviewed the characteristics and outcomes of 41 stage III and IV ucHL patients treated per physician preference with A+AVD as standard of care between 3/2010 and 12/2019. Treatment consisted of 1.2 mg/kg of BV and standard dose AVD, intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. All patients received support with granulocyte colony stimulating factor. Results: At time of treatment with A+AVD, median age was 38 (range 18-54 years) and IPS was 0-3 in 56% of patients. Overall, 95.1% of patients received 6 cycles of A+AVD, with a range of 3-6 cycles. During therapy, 19.5% of patients developed febrile neutropenia, 68.3% had at least one emergency department visit (median 2 visits, range 1-7), and 58.5% were hospitalized at least once (median hospital stay of 3 days, range 1-23). Furthermore, 4.9% of patients presented with grade ≥3 elevation of lipase, 4.9% grade ≥3 elevation of alanine aminotransferase, 9.8% deep vein thrombosis and 7.3% pulmonary embolism. Peripheral neuropathy (PN) occurred in 78% of patients, including grade ≥3 in 12.2%. Due to various toxicities, 22% of patients required at least one dose reduction of BV (median 5 reductions, range 2-7) and 46.3% had a least one dose omission of BV (median 4 omissions, range 1-10). At a median follow-up (FU) of 12.65 months (range: 5.91-85.97), 87.5% of patients had partial or complete improvement of their PN. The median delay of completion of 6 cycles of A+AVD was 8 days (range -1 to 35). The end-of-therapy PET/CT showed Deauville score of 1-3 in 85.3% of patients, 4 in 2.4% and 5 in 12.2%. However, only one patient relapsed 5 months after completion of 4 cycles of A+AVD and another relapsed 6 months after completion of 6 cycles. Both patients were still alive at last FU. The median PFS was not reached and 12-months PFS was 96.0% (95% confidence interval [CI], 88.6-100). Conclusions: In real-world experience, A+AVD is a highly effective treatment strategy for patients with advanced-stage ucHL. In light of its toxicity profile, strategies aimed at improving its safety are needed.

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Detection of Double Hit and Triple Hit Cytogenetics at Relapse Identifies a Very High Risk Subset of Relapsed/Refractory Multiple Myeloma Patients

Blood ◽

10.1182/blood-2021-152810 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2706-2706

Author(s):

Charanpreet Singh ◽

Sreejesh Sreedharanunni ◽

Vandana Panakkal ◽

Aditya Jandial ◽

Arihant Jain ◽

...

Keyword(s):

Multiple Myeloma ◽

High Risk ◽

Real World ◽

Cell Transplant ◽

Previous Exposure ◽

Entire Cohort ◽

Real World Setting ◽

Double Hit ◽

Active Disease

Abstract INTRODUCTION mSMART classifies high-risk Multiple Myeloma patients into Double Hit and Triple Hit Myeloma (DH/THM) on the basis of the number of high-risk cytogenetic abnormalities detected. While cytogenetics at diagnosis helps in the decision-making process regarding initial therapy, their role in relapsed MM is not very well studied. We aimed to study the clinical profile and outcomes of patients with DH/THM detected at relapse in a real-world setting. METHODS The case records of all relapsed multiple myeloma patients requiring active therapy between January 2018 and December 2020 were identified. All patients underwent bone marrow examination and repeat FISH cytogenetic analysis. The diagnosis of double hit and triple hit myeloma was based on mSMART classification (Presence of two or more of the following: IgH-FGFR3 translocation, IgH-MAF translocation, TP53 deletion, gain of chromosome 1q). Their case records were retrieved and information regarding baseline characteristics, therapy and outcomes was noted. RESULTS A total of 17 patients were diagnosed with DH/THM at relapse during the study period. Median age of the cohort was 59 years with almost an equal number of male and female patients (M=9; F=8). Renal failure (serum creatinine >2.0mg/dl) was seen in 8 patients (47.1%), while bone lesions, anemia (Hemoglobin <10gm/dl) and hypercalcemia (serum calcium >12mg/dl) were seen in 12 (70.6%), 12 (70.6%) and 6 (35.3%) patients respectively. Five patients (29.4%) fulfilled the criteria for plasma cell leukemia. Twelve patients (70.6%) were in first relapse, while 3 patients were diagnosed at second relapse and 1 patient each at 3 rd and 5 th relapse respectively. All but 2 patients had received Bortezomib previously (N=15; 88.2%). Eleven patients (64.7%) had previous exposure to Lenalidomide and 8 patients (47.1%) had previous exposure to Thalidomide. Two patients had previously undergone autologous hematopoietic cell transplant. Median follow-up prior to diagnosing DH/THL was 28 months (Range- 5-89 months). All patients had gain of 1q with at least 3 copies, while 12 patients (70.6%) had 4 or more copies. The most common cytogenetic combination was IgH-FGFR3 translocation with gain of 1q which was seen in 10 patients (58.8%). This was followed by co-occurrence of TP53 deletion with gain of 1q in 5 patients (29.4%). Two patients (11.8%) had triple hit myeloma. Seven patients (41.2%) died within the first month of relapse and a further 3 patients died during the next month. Of the 10 patients who received at-least 1 cycle of therapy, 8 received triplet therapy with the combination of a proteasome inhibitor and an Immunomodulator, one patient received doublet with Lenalidomide and dexamethasone and one patient received Daratumumab based quadruplet therapy. Bortezomib based therapy was used in 5 patients and 4 patients received Carfilzomib based therapy. None of the patients underwent a 2 nd auto transplant. Two patients achieved VGPR or better with therapy. Of the 7 evaluable patients, 5 re-relapsed during follow up. The follow up of entire cohort ranged from 0 to 29 months. Sixteen patients (94.1%) died during follow up. The most common cause of death was progressive/active disease (9 patients, 56.3%) followed by a combination of active disease with sepsis (4 patients, 25%). Median OS was 1 month for the entire cohort. DISCUSSION The outcome of DH/THM at relapse is associated with an aggressive presentation and poor outcomes in the real-world setting. These patients are candidates for early aggressive or novel therapy or clinical trials. Disclosures No relevant conflicts of interest to declare.

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