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The paper presents a case report of PET-adapted therapy of primary refractory classical Hodgkin’s lymphoma, stage ІІАХ, in a female patient with absolute lymphopenia prior to chemotherapy. It also provides literature review on the choice of clinical management for similar categories of patients. Nivolumab was prescribed to the patient in February 2019 due to Hodgkin’s lymphoma progression after the failure of 4 chemotherapy lines including brentuximab vedotin. A bulk of mediastinal lymph nodes was exposed to radiation. Complete metabolic response was retained 18 months after nivolumab therapy start and 6 months after its discontinuation. The initial lymphopenia in this patient with primary refractory Hodgkin’s lymphoma did not interfere with the realization of full clinical effect of nivolumab.

Introduction Brentuximab vedotin is a monoclonal antibody drug conjugate used for the treatment of patients with Hodgkin lymphoma. Hypersensitivity reactions to brentuximab vedotin may include cutaneous, cardiovascular, respiratory, gastrointestinal and neurological signs and symptoms. Case report We present the case of a 23-year-old Mexican female with stage IV progressive classical nodular sclerosing Hodgkin lymphoma who received multiple previous chemotherapy regimens. Brentuximab vedotin at 1.8 mg/kg (180 mg total dose), for 21-day cycles was indicated. Within 5 min of infusion of the 5th cycle of brentuximab, she developed severe anaphylaxis (hives, angioedema, diaphoresis, tachycardia, dyspnea, hypoxemia and loss of consciousness), which was successfully controlled with epinephrine, steroids and antihistamines. Management and outcome: Intradermal skin test at a concentration of 0.1 mg/ml was positive. Due to the severity of the symptoms and the lack of access to alternative treatments, we performed a desensitization protocol. A total of 180 mg of brentuximab was given in three bag solutions in 12 steps, with an initial concentration dose of 1/100 of the total dose in a course of 5.56 h with no hypersensitivity reactions. Discussion Severe anaphylaxis has been reported in 1.2% of patients receiving brentuximab vedotin. Patients who are treated by rapid drug desensitization with their first option therapy present a favorable survival rate with better cost-effectiveness in comparison to second-line treatment.

A 38 years old male patient of Arab origin was transferred to our hospital in 2016 suffering from a relapse of Hodgkin's lymphoma (HL), which was confirmed by a cervical lymph node biopsy. The pati...

Nivolumab is a monoclonal antibody against programmed cell death protein-1 which is assessed in the group of immune checkpoint inhibitors. It may lead to immune-related adverse events. In this article, we report a 38-year-old male patient diagnosed with seronegative arthritis after nivolumab therapy. This case supports that clinicians should be attentive for immune-related adverse events after use of immune checkpoint inhibitors.

Acute pulmonary toxicity associated with brentuximab appears to be a rare but serious adverse effect that can be potentially fatal. We report the case of a twenty-nine-year-old female with Hodgkin’s lymphoma who was treated with brentuximab and later presented with severe acute pulmonary toxicity; she improved after the discontinuation of brentuximab and administration of antibiotics and glucocorticoid therapy. Currently there is very little data in the literature in regard to the clinical manifestations and characteristics of patients taking brentuximab and the potential development of acute severe pulmonary toxicity, as well as the appropriate therapeutic approach, making this particular case of successful treatment and resolution unique.

Background & Aims. Most children with Hodgkin’s lymphoma (HL) can be cured irrespective of the disease stage using modern risk adapted protocols. But 3–5 % of children develop relapse of the disease or refractoriness to the treatment performed. The aim of the study was to perform a comparative analysis of ViGePP vs ICE antitumor treatment regimens in patients with relapsed and refractory Hodgkin’s lymphoma, as well as to evaluate the need in auto-HSCT and the site for a combined chemoradiation therapy in this patient population. Methods. From June, 2003, till December, 2014, 35 patients with relapsed (18) and refractory (17) HL received chemotherapy based on two regimes: ICE (n = 14; 40 %) and ViGePP (n = 14; 40 %). 7 (20 %) children were switched to another regimen due to a poor antitumor response to the first two courses of chemotherapy. Results. The direct effectiveness of the therapy was significantly higher in patients on ViGePP as compared to ICE irrespective of the disease status (relapsed or refractory). A complete response was achieved more often in those children with relapse HL whose initial treatment included radiation therapy. Higher survival rates were registered in girls, as well as in children with a complete overall response to the antirelapse therapy. In case of relapses, delayed treatment effects (disease free survival and overall survival) were higher in children treated with 4 courses of ViGePP than 2 courses of ICE. High-dose chemotherapy with subsequent auto-HSCT is not able to overcome refractoriness to the chemotherapy. Conclusion. Children with relapsed and refractory HL need an intensive antirelapse chemotherapy with subsequent HDC and auto-HSCT to achieve CR.

Brentuximab vedotin is a promising antibody–drug conjugate (ADC) targeting CD30 of tumor cells. It selectively delivers monomethyl auristatin E (MMAE) into CD30-expressing cells and induces tumor cell apoptosis. Various clinical trials have provided evidence that it is effective in relapsed or refractory Hodgkin’s lymphoma (HL), and it has also shown its advantages in other CD30-positive lymphomas. In this review, we focus on the structure, mechanisms, and pharmacokinetics of brentuximab vedotin. We also summarize clinical trials with brentuximab vedotin and make recommendations for brentuximab vedotin in the treatment of relapsed or refractory HL.

Nivolumab in a patient with refractory Hodgkin’s lymphoma after allogeneic stem cell transplantation

Advanced-stage Hodgkin's lymphoma (HL) has become a curable disease in the majority of patients. Despite this, about 20% of these patients relapsed or are primary refractory to the first-line treatment and high-dose chemotherapy (HDC) and autologous (Auto) hematopoietic progenitor cells transplantation (HPCT) are considered a therapeutic option.The authors reviewed HDC and HPCT treatment strategies in recurrent or refractory HL patients, with the goal of providing an overview of this approach.Patients younger than 60-65 years with relapsed disease or refractory to first-line therapy should receive a second-line chemotherapy, followed by HDC and Auto-HPCT. Progression-free and overall survival results are significantly better when a second remission or a minimal disease status is achieved before Auto-HPCT, and demonstrate that this strategy is able to cure more than half of the advanced HL patients. Myeloablative allogeneic HPCT (Allo-HPCT) has been employed in advanced phases of the disease, but there have been significant concerns due to treatment-related mortality (TRM). The safety of allogeneic transplantation has improved with the use of reduced-intensity allogeneic (RIC-Allo) HPCT strategies. Despite early favorable results, mature results of RIC-Allo available in the literature are consistent in demonstrating a lack of long-term disease control.

Purpose Hodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population. Patients and Methods Panobinostat 40 mg was administered orally three times per week. The primary end point was objective response rate (ORR) based on investigator assessment of radiologic imaging. Secondary end points included ORR by independent central review, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses were performed. Results The 129 treated patients (median age, 32 years; range, 18 to 75 years) were heavily pretreated with a median of four (range, two to seven) prior systemic regimens, and 41% did not respond to the regimen immediately preceding panobinostat. Tumor reductions occurred in 96 patients (74%). Objective response was achieved by 35 patients (27%), including 30 (23%) partial responses and five (4%) complete responses. The median TTR was 2.3 months, median DOR was 6.9 months, and median PFS was 6.1 months. The estimated 1-year overall survival rate was 78%. Common nonhematologic adverse events (AEs)—diarrhea, nausea, vomiting, and fatigue—were generally grade 1 and 2. Most common grade 3 and 4 hematologic AEs—thrombocytopenia, anemia, and neutropenia—were manageable. Early reductions in thymus and activation-regulated chemokine were observed in patients achieving complete or partial response. Conclusion In the largest, prospective, multicenter, international trial conducted in heavily pretreated patients with HL who relapsed or were refractory to ASCT, panobinostat monotherapy demonstrated antitumor activity, resulting in durable responses.

GISL recently conducted an exhaustive survey of 1078 patients with Hodgkin's Lymphoma (HL) enrolled between 1988 and 2002 in different prospective trials. Treatment failure was observed in 82 out of 1078 patients; of these 82 patients with refractory HL, complete information was available for 72, who form the evaluable population of the present study. After the initial therapy failure, 51 patients were treated with conventional salvage chemotherapy (CC) (n = 24) or high-dose chemotherapy (HDC) (n = 27); 4-year overall survival (OS) was 81% in the HDC group versus 38% in the CC group (P = 0.019). The remaining 21 patients had rapidly progressive disease and died. After a median follow-up of 2.8 years, the projected OS for all 72 patients is 58 and 49% at 3 and 5 years, respectively. Age45 years, the absence of systemic symptoms and a PS1 predicted a significantly longer OS. Interestingly, the majority of patients with two or three negative prognostic factors did not receive potentially curative therapy. In conclusion, HDC seems to be a reasonable option for selected patients with refractory HL, although the majority of them did not receive a transplant. Finally, patients with a high-risk score had little chance of receiving potentially curative treatment.

Failure to initiate treatment remains a challenge in Hodgkin’s lymphoma (HL). For years, chemotherapy and stem cell transplantation salvaged less than half of relapses. Nowadays, positron emission tomography can predict the outcome under treatment. Two targeted agents are dramatically improving therapy, alone or in association with chemotherapy or stem cell transplantation. Brentuximab vedotin is an immunoconjugate anti-CD30 and anti-programmed death 1 nivolumab induces blockade of immune checkpoint. How to use them are discussed in the context of relapses/refractory HL.

Successful mobilization with plerixafor and autologous hematopoietic SCT in a patient with refractory Hodgkin's lymphoma and Gaucher disease

Myeloablative allogeneic HCT salvages some patients (pts) with relapsed and refractory HL but has a high treatment-related mortality (TRM). NST/RIC conditioning regimens attempt to lower TRM, in particular after previous autotransplants. We studied the outcomes of 146 patients after unrelated donor (URD) HCT with NST/RIC conditioning for relapsed and refractory HL between 1999 and 2004 reported to the CIBMTR. NST/RIC was defined following established CIBMTR criteria as TBI < 500 cGy, busulfan < 9 mg/kg, melphalan ≤ 150 mg/m2 (RIC) or fludarabine without busulfan/melphalan, TBI = 200 cGy (NST). Median (range) age was 30 yrs (13–53), 69% had a Karnofsky score (KPS) ≥ 90%, 95% patients had ≥ 3 chemo regimens prior to HCT and 89% had undergone prior autotransplant. At transplant 57 (40%) had chemosensitive disease and 74 (51%) were chemoresistant. Conditioning was RIC in 95 (65%) and NST in 51 pts (35%). At a median follow-up of 25 mo (3–64) the probability of day 100 mortality was 18% (95% CI, 12–24%), acute GVHD grade 2–4 was 61% (95% CI, 51–70%), cGVHD at 2 years was 69% (95% CI, 60–77%) and TRM at 2 years was 33% (95% CI, 25–41%). Probability of progression free survival (PFS) was 31% at 1 year and 20% at 2 years. Probability of overall survival (OS) was 56% at 1 year and 38% at 2 years (fig 1). Relapse/progression was rare after 2 years with a plateau in the survival curve. Presence of extranodal disease (relative risk [RR] 2.43, 95% CI, 1.30–4.54, p=0.006) and KPS Figure: 1 Figure: 1.

6651 Background: High dose chemotherapy and autologous stem cell transplantation (ASCT) is the most effective treatment for recurrent or refractory Hodgkin’s lymphoma (HL). Disease recurrence is st...

Background Reports dealing with clinical outcomes of classical Hodgkin's lymphoma in low- to middle-income countries are scarce and response to therapy is poorly documented. This report describes the characteristics and clinical outcomes of patients with classical Hodgkin's lymphoma from a single institution in Latin America. Method A retrospective study was conducted over ten years of patients with classical Hodgkin's lymphoma treated at a referral center. Progression-free and overall survival rates were estimated by Kaplan–Meier analysis. The univariate Cox regression model was used to estimate associations between important variables and clinical outcomes. Main results One hundred and twenty-eight patients were analyzed. The mean age was 28.5 years. The five-year progression-free and overall survival were 37.3% and 78.9%, respectively. Of the whole group, 55 (43%) were primary refractory cases. Only 39/83 (47%) patients with advanced disease vs. 34/45 (75.6%) in early stages (p-value = 0.002) achieved complete remission. Those with advanced disease had a five-year overall survival of 68.7% vs. 91.8% for early disease (p-value = 0.132). Thirty-one patients relapsed (24.2%) and 20 (64.5%) received a transplant. The hazard ratio for progression with bone marrow infiltration was 2.628 (p-value = 0.037). For death, an International Prognostic Score ≥4 had a hazard ratio of 3.355 (p-value = 0.050) in univariate analysis. Two-thirds of classical Hodgkin's lymphoma patients diagnosed at advanced stages had a low progression-free survival but an overall survival similar to high-income countries. Conclusion Patients diagnosed with classical Hodgkin's lymphoma in Northeastern Mexico had a significantly low progression-free survival rate and presented with advanced disease, underscoring the need for earlier diagnosis and improved contemporary therapeutic strategies in these mainly young productive-age Hodgkin's lymphoma patients.