Relapse After Early-Stage, Favorable Hodgkin Lymphoma: Disease Characteristics and Outcomes With Conventional or High-Dose Chemotherapy

PURPOSE We evaluated disease and treatment characteristics of patients with relapse after risk-adapted first-line treatment of early-stage, favorable, classic Hodgkin lymphoma (ES-HL). We compared second-line therapy with high-dose chemotherapy and autologous stem cell transplantation (ASCT) or conventional chemotherapy (CTx). METHODS We analyzed patients with relapse after ES-HL treated within the German Hodgkin Study Group HD10+HD13 trials. We compared, by Cox proportional hazards regression, progression-free survival (PFS) after relapse (second PFS) treated with either ASCT or CTx and performed sensitivity analyses with overall survival (OS) from relapse and Kaplan-Meier statistics. RESULTS A total of 174 patients’ disease relapsed after treatment in the HD10 (n = 53) and HD13 (n = 121) trials. Relapse mostly occurred > 12 months after first diagnosis, predominantly with stage I-II disease. Of 172 patients with known second-line therapy, 85 received CTx (49%); 70, ASCT (41%); 11, radiotherapy only (6%); and 4, palliative single agent therapies (2%). CTx was predominantly bleomycin, etoposide, doxorubicin cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP [68%]), followed by the combination regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine (19%), or other regimens (13%). Patients aged > 60 years at relapse had shorter second PFS (hazard ratio [HR], 3.0; P = .0029) and were mostly treated with CTx (n = 33 of 49; 67%) and rarely with ASCT (n = 8; 16%). After adjustment for age and a disadvantage of ASCT after the more historic HD10 trial, we did not observe a significant difference in the efficacy of CTx versus ASCT for second PFS (HR, 0.7; 95% CI, 0.3 to 1.6; P = .39). In patients in the HD13 trial who were aged ≤ 60 years, the 2-year, second PFS rate was 94.0% with CTx (95% CI, 85.7% to 100%) versus 83.3% with ASCT (95% CI, 71.8% to 94.8%). Additional sensitivity analyses including OS confirmed these observations. CONCLUSION After contemporary treatment of ES-HL, relapse mostly occurred > 12 months after first diagnosis. Polychemotherapy regimens such as BEACOPP are frequently administered and may constitute a reasonable treatment option for selected patients with relapse after ES-HL.

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Fludarabine, Cyclophosphamide and Rituximab (FCR) Related Prolonged Cytopenia Is Frequent and Adverse Factor Affecting Survival of Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v120.21.1790.1790 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1790-1790

Author(s):

Petra Obrtlikova ◽

Anna Jonasova ◽

Magda Siskova ◽

Eduard Cmunt ◽

Adela Berkova ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

High Dose ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Significant Difference

Abstract Abstract 1790 Background: The immunochemotherapy regimen composed of fludarabine, cyclophosphamide and rituximab (FCR) has emerged as highly effective frontline or second line therapy for chronic lymphocytic leukemia (CLL). This regimen may be however associated with prolonged cytopenia and the risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Aims and methods: In our retrospective single center analysis, we evaluated the efficacy and the toxicity of FC or FCR regimen in unselected population of CLL patients with treatment indication. The overall survival (OS) and progression free survival (PFS) was calculated for all patients as intent to treat analysis. The prolonged cytopenia was defined as cytopenia (grade 2–4 according to CTCAE v.4 ) developing during of after the last cycle of FC/FCR and persisting two or more months. Cytopenia was evaluated in patients with follow-up at least 6 months after this treatment. Patients were excluded from analysis of cytopenia if they underwent immediate other treatment (antibody maintenance, high dose therapy with autologous stem cell transplantation (ASCT) consolidation, or they received other therapy due to unsatisfactory response to FCR). Patients with missing laboratory data after FC(R) were also excluded. Kaplan Maier curves for PFS and OS were calculated and log rank test was used for survival comparison. Results: Altogether, 252 patients started the treatment with FC or FCR in the years 2000–2012 at our institution. There were 86 (34%) women and 166 (66%) men with a median age of 62 years (31–87) at the time of FC(R) therapy. 52 (21%) pts received FC regimen, including 40 pts treated in first line therapy and 12 pts in second line therapy. FCR therapy was administered in 200 pts (79%): 153 pts received FCR as first line therapy, 38 pts as second line therapy and 8 pts as third or fouth line therapy. The median number of FC cycles was 5 (1–8) with or without R. The estimated OS for the first line therapy was 87,5% in FCR group vs 80% at 3y in FC group (p ns) (Hallek,CLL8: 87% vs 83%) and PFS was 70% in FCR group vs 50% in FC group (p=0,004) with the median of follow-up 45 months. Altogether 184 pts fulfill the criteria for cytopenia analysis. The most frequent immediate subsequent therapy considered as exclusion for this analysis was ASCT consolidation (n 20). Out of 184 pts, 146 recieved FC(R) as 1st line treatment and 38 subsequent therapy. The prolonged cytopenia was observed in 54 pts (29%), 42 (29%) in 1st line group and 12 (32%) in subsequent line group. Median duration of cytopenia was 8 m (2–65), 29 out of 54 patients have had persistent cytopenia at the time of last follow up. The cumulative probability to develop cytopenia was 30.3% at 2y among all pts and 29.7% among first line FCR treated pts. There was no significant difference between FC and FCR treated pts. Eleven pts developed MDS/AML, 7 cases were observed in the followed group of 184 pts (with probability 6.1% at 6y), in all cases the cytopenia preceded the MDS onset, 6y probability to develop MDS was 25.2% for patients who develop prolonged cytopenia after FC(R). Moreover 2 MDS and 1 AML were observed among 20 pts treated with ASCT (6y probability 5.6%, 8y probability 22.5%). The OS probability from 1stcycle of FC(R) was significantly better for pts without cytopenia (75.5% vs 57.5% at 5y, p<0.005), nonsigificant trend was observed if only first line FCR pts were analyzed (88% vs 85%). The median survival for the MDS pts from the time of MDS dg was 6 months only. Conclusions: Although the FCR is the best available standard treatment option for CLL pts, it is associated with prolonged cytopenia in 30% of cases. These patients with prolonged cytopenia afte FC(R) have considerably high probability (25.2%) to develop MDS and they have worse OS compared to pts without cytopenia. Disclosures: No relevant conflicts of interest to declare.

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Phase II Trial of Pembrolizumab Plus Gemcitabine, Vinorelbine, and Liposomal Doxorubicin as Second-Line Therapy for Relapsed or Refractory Classical Hodgkin Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.21.01056 ◽

2021 ◽

pp. JCO.21.01056

Author(s):

Alison J. Moskowitz ◽

Gunjan Shah ◽

Heiko Schöder ◽

Nivetha Ganesan ◽

Esther Drill ◽

...

Keyword(s):

Hodgkin Lymphoma ◽

Phase Ii ◽

Liposomal Doxorubicin ◽

Hematopoietic Cell Transplantation ◽

Brentuximab Vedotin ◽

High Dose ◽

Second Line ◽

Classical Hodgkin Lymphoma ◽

Second Line Therapy ◽

Line Therapy

PURPOSE We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550 ). METHODS Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m2 IV, days 1 and 8), vinorelbine (20 mg/m2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m2, days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT. RESULTS Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months). CONCLUSION Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT.

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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1338. Analysis of Prescription Guideline Adherence in Pediatric Outpatient Pneumonia Treatment

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.1520 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S680-S681

Author(s):

Carly Heck ◽

Judith Martin ◽

Marcia Kurs-Lasky

Keyword(s):

Drug Allergy ◽

Health Concern ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy ◽

Comparison Results ◽

Significant Difference ◽

Recommended Therapy

Abstract Background Background: Antibiotic resistance is a major public health concern. A modifiable intervention is outpatient antibiotic stewardship. The goal of this study was to review the electronic health records (EHR) of children diagnosed with community acquired pneumonia (CAP) to compare patients who received non-guideline concordant therapy with those prescribed recommended therapy. Methods Methods: This was a retrospective chart review of 300 children (6 months to 6 years old) with an outpatient diagnosis of CAP between July 2017 and June 2019. 45 Children’s Hospital of Pittsburgh (CHP) and UPMC Children’s Community Pediatrics (CCP) practices were included. CHP practices are academic-based with trainees involved in visits, while CCP practices do not include trainees. First-line recommended therapy was defined as amoxicillin, second-line therapy as azithromycin or amoxicillin-clavulanate, and all other prescriptions were defined as other. Patients prescribed first-line therapy were compared to patients with second-line therapy or other. If first-line therapy was not prescribed, the EHR was manually reviewed for justification. If drug allergy was listed, the medication allergy and type of reaction were recorded. Results Results: In this study the minority of children (43%) were prescribed first-line therapy. This group was younger (57 vs. 63 months of age), more likely to be Non-white (80%), and seen at the CHP locations than those prescribed non-guideline concordant therapy. The average symptom duration was shorter, heart rate and respiratory rate were higher and the presence of fever was more common in the first-line therapy group. Justification for non-guideline therapy was most often reported as to provide coverage for atypical organisms. The most common drug allergy recorded was amoxicillin, and urticaria with unknown timing was the most common type of reaction. Demographics Comparison Results Justification for Second-line / Other Therapy and Drug Allergy Results Conclusion This project observed a high proportion of children being prescribed non-guideline concordant therapy for a diagnosis of CAP. Age, race, practice location, and severity of illness measures showed a statistically significant difference between groups. This study highlights the importance of education which reviews the current guidelines and the most likely pathogens for children with CAP. Disclosures All Authors: No reported disclosures

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Optimizing Second-Line Therapy for Hodgkin Lymphoma: A Work in Progress

Journal of Clinical Oncology ◽

10.1200/jco.21.01552 ◽

2021 ◽

pp. JCO.21.01552

Author(s):

Nancy L. Bartlett

Keyword(s):

Clinical Practice ◽

Hodgkin Lymphoma ◽

Relevant Literature ◽

Second Line ◽

Clinical Context ◽

Second Line Therapy ◽

Case Presentation ◽

Line Therapy ◽

Management Approaches ◽

Grand Rounds

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.

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Determining the efficiency of the Imatinib mesylate and monitoring of relapse and emergence of IM resistance in Algerian adult patients with Chronic Myeloid Leukaemia

South Asian Journal of Experimental Biology ◽

10.38150/sajeb.8(3).p103-108 ◽

2019 ◽

Vol 8 (3) ◽

pp. 103-108

Author(s):

Amel Sebaa ◽

Mustapha Diaf ◽

Sakina Cherif Touil

Keyword(s):

Chronic Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Imatinib Mesylate ◽

Second Generation ◽

Adult Patients ◽

Second Line ◽

Second Line Therapy ◽

Molecular Responses ◽

Line Therapy ◽

Significant Difference

Imatinib mesylate (IM) shows remarkable clinical activity in patients with Chronic Myeloid Leukaemia (CML). Patients who fail to respond to IM or those who lose their response should be treated with second-generation tyrosine kinase inhibitors (TKIs). The aim of this study was to determine the efficiency of the Indian IM generic (Imatib*CIPLA), and to monitor relapse and emergence of IM resistance. Two hundred and seven adult patients from the Northwestern region of Algeria were diagnosed as CML in chronic phase (CP) and were treated with an Indian generic of IM at 400 mg/day. The IM 600 mg treatment and second-line therapy were prescribed after failure of treatment. Molecular Analysis was performed and BCR-ABL/ABL ratios were determined and standardised according to the international scale using 0.47 as conversion factor. Our findings showed a significant difference in major molecular response (MMR) for patients treated with IM 600 mg compared to IM 400 mg (51.7% vs. 37.6%, p<0.001). In the second line therapy group, there was a significant improvement of MR4.5 compared to the IM group (7.7% vs. 32.6%, p=0.039). Likewise, no significant relationship was found between the median duration of second-generation TKIs deep response and IM 400 mg/day regarding the MR4 (11 vs. 26.5 months, p=0.107) and MR4.5 (20 vs. 32.5 months, p=0.203). The Indian IM generic molecule (Imatib*CIPLA), has shown its efficiency in achieving major and deep molecular responses. Patients treated with the second-generation TKIs showed deep molecular responses with fewer relapses in a shorter median time than those treated with IM.

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