PD-1 Blockade After Avelumab in Relapsed/Refractory Classical Hodgkin Lymphoma

BackgroundAnti-PD-1 directed therapy is safe and effective in patients with relapsed/refractory (r/r) cHL and is currently being studied in the frontline setting. There are currently little data regarding the safety and efficacy of PD-1 blockade after prior PD-L1 blockade with agents such as avelumab.MethodsThis is a retrospective case series evaluating r/r cHL patients treated with avelumab who subsequently received at least 1 dose of PD-1 blockade. Primary objective is efficacy as measured by overall response rate. Secondary objectives include duration of response and time to progression on PD-1 blockade as well as safety as evaluated by incidence and severity of immune-related adverse events (irAE) with PD-1 blockade.ResultsThere were 7 patients treated with PD-1 blockade after avelumab, of whom 4 were re-treated. The median follow-up was 46.8 months. At the time of PD-1 blockade initiation median age was 36.6 years, all patients had advanced stage, 1 patient had B symptoms, and 4 patients had extranodal disease. Patients received median 7 prior lines of therapy including avelumab. Median duration on anti-PD-1 treatment was 15.9 months. A response was observed in 86% of patients with median duration of response of 26.4 months and median time to progression of 22.2 months. Only 1 patient experienced an irAE (grade 2 pneumonitis).ConclusionOur study suggests that PD-1 blockade after PD-L1 blockade in r/r cHL appears safe and may be effective with durable responses observed in a subset of patients.     

Polatuzumab Vedotin for Relapsed/Refractory Aggressive B-cell Lymphoma: A Multicenter Post-marketing Analysis

IntroductionPolatuzumab vedotin is approved therapy in the United States for relapsed/refractory diffuse large B-cell lymphoma in combination with bendamustine and rituximab (Pola+BR). However, the safety and efficacy of Pola+BR outside of a clinical trial setting is unknown.Patients and MethodsWe analyzed use of pola-based therapy at 5 centers in the United States, including dose, response rates, progression-free survival (PFS), survival, and toxicity.ResultsSixty-nine patients with aggressive B-cell lymphoma, including 66 with diffuse large B-cell lymphoma/high-grade B-cell lymphoma and 84% refractory to prior therapy, were treated. Responses occurred in of 50%, including 24% complete response. Median duration of response was 5.1 months, PFS was 2.0 months, and survival was 5.3 months, at 4 months median follow-up. Inferior PFS was associated with prior refractory disease (median, 57 days vs. not reached; P = .003) and lack of response to Pola+BR (PFS, 27 days vs. 152 days; P < .001). Discontinuation owing to planned cellular therapy was seen in 36% and owing to toxicity occurred in 12%; unplanned hospitalizations occurred in 36%.ConclusionsWe conclude that commercial Pola is applied to highly refractory lymphomas at our centers, often with intent to bridge to subsequent therapy. Although some clinical benefit was observed, efficacy was inferior to clinical trial data, especially among those with refractory disease.     

PEP-C节拍化疗方案治疗复发和难治性非霍奇金淋巴瘤23例探讨

目的：评价PEP-C节拍化疗方案治疗复发和难治性非霍奇金淋巴瘤的疗效和不良反应。方法： 回顾性分析厦门大学附属中山医院采用PEP-C节拍化疗方案治疗的23例复发和难治性非霍奇金淋巴瘤患者的临床资料。结果： 所有23例患者均可评价疗效和不良反应, 完全缓解 （CR） 率30.4% （7/23）, 部分缓解率 （PR） 30.4% （7/23）, 总的客观有效率 （RR） 60.8% （14/23）。低度恶性非霍奇金淋巴瘤与中高度恶性非霍奇金淋巴瘤有效率分别为81.8% （9/11）、 41.7% （5/12）, 完全缓解率分别为45.5% （5/11）、16.7% （2/12）（P<0.05）。国际预后指数 （IPI） 低危组 （IPI评分0～2分） 与高危组 （IPI评分3～5分） 有效率分别为60.0% （9/15）、62.5% （5/8）, 完全缓解率分别为33.3% （5/15）、 25.0% （2/8）（P>0.05）。主要不良反应为骨髓抑制、 恶心呕吐及腹泻, 经过治疗均可恢复, 无治疗相关死亡。结论： PEP-C节拍化疗方案对于复发难治性非霍奇金淋巴瘤疗效肯定, 不良反应较低, 特别适合不能耐受强烈化疗的患者, 值得在更多病例中进一步研究。     

Outcomes After Salvage Autologous Hematopoietic Cell Transplant for Patients With Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience

BackgroundThe role of salvage autologous hematopoietic cell transplantation (sAHCT2) for patients with relapsed/refractory multiple myeloma (RRMM) in the era of modern therapeutics is unclear. As prospective data is limited, we conducted a retrospective analysis to determine the outcomes of sAHCT2.Patients and methodsWe conducted a single-institution, retrospective analysis of patients who received sAHCT2 at The Ohio State University from 2000 to 2018. Patients who received a second transplant as part of a planned tandem or autologous-allogeneic transplant were excluded.ResultsFifty-seven patients were treated with sAHCT2. Patients had a median of 2 lines of therapy after AHCT1 prior to their sAHCT2; 70% had prior immunomodulatory imide drugs, 82% had prior proteasome inhibitor, and 20% had prior anti-CD38 monoclonal antibodies as part of re-induction therapy. Forty-two percent of patients attained ≥VGPR prior to sAHCT2. Seventy-four were treated with melphalan 200 mg/m² as conditioning regimen before infusion of a median of 3.8 × 10⁶ CD34+ cells/kg. Fifty-eight percent patients had maintenance therapy and 81% patients attained CR/VGPR as the best response after sAHCT2. The median PFS and OS after sAHCT2 were 1.6 and 3.6 years, respectively. On multivariable analysis, high-risk cytogenetics, not having attained CR/VGPR, and having more than 2 lines of therapy post-AHCT1 were associated with inferior PFS. Melphalan 140 mg/m² compared to melphalan 200 mg/m² and no maintenance therapy compared to maintenance therapy were not associated with inferior PFS. There was no transplant-related mortality in this patient cohort.ConclusionsFor MM patients deriving durable remission after their AHCT1, sAHCT2 was safe and resulted in deep and durable remissions.     

A Systematic Review of Treatments of Relapsed/Refractory Mantle Cell Lymphoma

A systematic review was conducted to evaluate the clinical effectiveness and safety of treatments for patients with relapsed/refractory mantle cell lymphoma (MCL) unsuitable for intensive treatment. The criteria for inclusion of the trials were established before the review. A search of Medline, Embase, and the Cochrane library databases was conducted to identify phase II or III randomized controlled trials (RCTs), reported from January 1, 1994 to May 29, 2016. Relevant conference abstracts, citation lists from the included articles, published guidelines, and on-going clinical trial databases were also searched. Studies were included if they had evaluated any single agent or combination of treatments for adult patients with relapsed/refractory MCL who had received ≥ 1 previous line of therapy. Seven RCTs were identified. Only 1 treatment appeared in > 1 trial; therefore, the results from each trial could not be quantitatively pooled for meta-analysis. The lack of common comparators, differences in baseline characteristics and inclusion and exclusion criteria, and variances in the response criteria used to measure outcomes made comparison of the results difficult. Although the direction of effect for progression-free survival (PFS) and overall survival (OS) was in favor of the experimental drug in all trials, the difference in PFS was statistically significant in 5 and OS in 2. None showed statistical significance for both. A noticeable lack of RCTs evaluating treatments for patients with relapsed/refractory MCL made meaningful comparisons of effectiveness across trials rather difficult. This trend continues, because all, bar 1, of the 85 ongoing trials in this area are single-arm studies. RCTs are required to enable better evaluation of the optimal treatment regimen for this group of patients.     

Outcomes of VD-PACE With Immunomodulatory Agent as a Salvage Therapy for Relapsed/Refractory Multiple Myeloma

BackgroundAggressive relapsed/refractory multiple myeloma (RRMM) often requires salvage cytotoxic chemotherapy. We evaluated the efficacy and toxicity of VD-PACE (bortezomib, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, etoposide) with an immunomodulatory agent (IMiD) in RRMM.Patients and MethodsWe retrospectively reviewed the effectiveness and tolerability among 30 patients with RRMM receiving ≥ 1 cycle of VD-PACE + IMiD between January 2012 to April 2019.ResultsOf 30 patients, 26 (86%) had myeloma double refractory to protease inhibitors and IMiDs, and had received a median of 3 lines prior of therapy. The overall response rate was 67.7%, 13% patients experienced complete remission or better, and 13% experienced very good partial response. Median progression-free and median overall survival were 11 and 26 months, respectively. The most common grade 3 or higher adverse events were hematologic events, which were manageable.ConclusionVD-PACE + IMiD is an effective and tolerable salvage treatment for RRMM, with an impressive response rate in pretreated RRMM.     

Outcomes of Transplant-Eligible Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After Second-Line Salvage Chemotherapy: The Gustave Roussy Experience

IntroductionAfter failure of frontline therapy, patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL) that does not respond to first-line salvage chemotherapy can be recommended second-line salvage chemotherapy. The available literature in this regard is weak, although many centers routinely offer this type of second-line salvage chemotherapy to their patients.Patients and MethodsThis retrospective study included transplant-eligible patients with RR-DLBCL treated at Gustave Roussy between January 2008 and April 2020. Eligible patients were those who received second-line salvage chemotherapy using R-DHAP or R-ICE in patients who experienced an insufficient partial response, stable disease, or progressive disease in response to first-line salvage chemoimmunotherapy using an alternative regimen.ResultsForty-six RR-DLBCL patients received second-line salvage regimen, which yielded an objective response rate of 33%, median progression-free survival of 2.1 months, and overall survival of 11.4 months. Twelve patients proceeded to autologous stem-cell transplantation (ASCT), of whom 70% remained alive 1 year after ASCT. To explore the impact of transplantation, a multivariate analysis (excluding response to the first-line salvage regimen because this covariate was totally embedded within the transplantation covariate), ASCT was associated with progression-free survival (hazard ratio = 0.16; 95% confidence interval, 0.06-0.42) and overall survival (hazard ratio = 0.27; 95% confidence interval, 0.08-0.88).ConclusionSecond-line salvage chemotherapy with R-DHAP or R-ICE followed by ASCT leads to a favorable outcome in almost one third of patients with RR-DLBCL and offers a median overall survival of approximately 1 year. These data support the administration of second-line salvage chemotherapy followed by ASCT.     

GDP方案治疗复发和难治性非霍奇金淋巴瘤的疗效观察

目的 观察GDP方案(吉西他滨、顺铂、地塞米松)治疗复发和难治性非霍奇金淋巴瘤(NHL)的疗效和不良反应.方法 回顾性分析用GDP方案治疗的19例复发和难治性非霍奇金淋巴瘤患者的临床资料,包括治疗后缓解情况、复发率、生存率以及出现的不良反应.结果 19例患者均可评价疗效和不良反应,其中完全缓解(CR)5例,部分缓解(PR)5例,稳定(SD)4例,进展(PD)3例,总有效率为52.6%.1年总生存率为48.8%.主要不良反应为骨髓抑制,其中Ⅲ~Ⅳ度中性粒细胞减少发生率为15.8%,Ⅲ~Ⅳ度血小板减少发生率为21.1%,恶心呕吐反应一般对症治疗可恢复,无治疗相关死亡.结论 GDP方案治疗难治和复发性非霍奇金淋巴瘤疗效好,副作用可以耐受,是一种值得进一步推广的挽救治疗方案.     

Favorable Outcome After Adjuvant Involved-Field Radiotherapy After Autologous Hematopoietic Stem-Cell Transplantation in Patients With High-Risk Relapsed/Refractory Lymphoma: A Single-Center Experience

BackgroundPatients with refractory or relapsed lymphoma diagnosed with bulky disease at relapse or with residual disease after salvage treatment are considered to have a dismal outcome, even after autologous hematopoietic stem-cell transplantation, as a result of disease recurrence. To minimize the risk of relapse after receipt of a transplant, involved-field radiotherapy (IFRT) to sites of either bulky or localized residual disease has been utilized; however, the ideal timing for irradiation remains controversial. The aim of this study was to assess the safety and efficacy of IFRT in the early period after transplantation.Patients and MethodsWe retrospectively evaluated the outcome of 24 autografted patients with relapsed/refractory lymphoma who presented with bulky disease at relapse or who had a persistent localized residual mass after salvage treatment and consolidated with IFRT within 4 months after autografting.ResultsNo significant toxicity was noticed during the early postradiotherapy period, while graft function was not impaired. After a median follow-up of 3 years for survivors, 21 patients were alive, 19 of whom were event free, while 2 patients died of disease recurrence and 1 died of treatment-related myelodysplastic syndrome. The 3-year overall, lymphoma relapse-free, and event-free survival rates were 86%, 86%, and 82%, respectively.ConclusionTaking into consideration the poor-risk features of the study cohort, IFRT provided early after autologous hematopoietic stem-cell transplantation showed a safe and well-tolerated toxicity profile and demonstrated long-term effective tumor control, as reflected in the promising survival rates.     

Consolidative Radiotherapy After Autologous Stem Cell Transplantation for Relapsed or Refractory Diffuse Large B-cell Lymphoma

Introduction

We evaluated the role of consolidative radiotherapy (RT) for patients undergoing high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Real World Outcomes in Patients With Relapsed/Refractory Diffuse Large B-cell Lymphoma Receiving Palliative Intent Therapies

BackgroundOutcomes in patients with relapsed/refractory (R/R) diffuse large b-cell lymphoma (DLBCL) who are ineligible for and/or fail high-dose chemotherapy and autologous stem cell transplantation in the second line are poor. There is no preferred palliative-intent treatment for patients in this setting.Patients and MethodsA retrospective cohort study was performed using the nationwide de-identified electronic health record-derived Flatiron Health database. Event-free survival (EFS) and overall survival (OS) was evaluated for patients with R/R DLBCL who were ineligible for and/or failed autologous stem cell transplantation in the second line and received bendamustine, gemcitabine, or lenalidomide.ResultsThree hundred eighty-three patients were included. Therapy received was bendamustine in 158 patients, gemcitabine in 142 patients, and lenalidomide in 83 patients. The median EFS and OS for all patients was 4.1 months and 8.7 months, respectively. Compared with patients receiving bendamustine or gemcitabine, those receiving lenalidomide demonstrated significantly longer median EFS (6.8 vs. 3.8 months; P = .006) and median OS (15.4 vs. 7.7 months; P = .045). Survival outcomes were also improved for lenalidomide-treated patients specifically in the second- as well as third- or fourth-line settings.ConclusionUse of lenalidomide resulted in prolonged EFS and OS as compared with bendamustine or gemcitabine in this cohort of patients with R/R DLBCL receiving palliative therapy. This first large-scale analysis of real-world outcomes for this patient population may guide current clinical management as well as serve as a benchmark for survival outcomes in the standard-of-care setting, which may aid in the design of future clinical trials.     

Treatment Landscape of Relapsed/Refractory Mantle Cell Lymphoma: An Updated Review

Mantle cell lymphoma (MCL) accounts for nearly 2-6% of all non-Hodgkin lymphoma (NHL) cases, with a steady incidence increase over the past few decades. Although many patients achieve an adequate response to the upfront treatment, the short duration of remission with rapid relapse is challenging during MCL management. In this regard, there is no consensus on the best treatment options for relapsed/refractory (R/R) disease, and the international guidelines demonstrate wide variations in the recommended approaches. The last decade has witnessed the introduction of new agents in the treatment landscape of R/R MCL. Since the introduction of Bruton's tyrosine kinase (BTK) inhibitors, the treatment algorithm and response of R/R MCL patients have dramatically changed. Nevertheless, BTK resistance is common, necessitating further investigations to develop novel agents with a more durable response. Novel agents targeting the B-cell receptor (BCR) signaling have exhibited clinical activity and a well-tolerable safety profile. However, as the responses to these novel agents are still modest in most clinical trials, combination strategies were investigated in pre-clinical and early clinical settings to determine whether the combination of novel agents would exhibit a better durable response than single agents. In this report, we provide an updated literature review that covers recent clinical data about the safety and efficacy of novel therapies for the management of R/R MCL.