Rituximab, gemcitabine and oxaliplatin: an effective salvage regimen for patients with relapsed or refractory B-cell lymphoma not candidates for high-dose therapy.

BACKGROUND: High-dose therapy (HDT) with stem-cell support is the reference treatment for relapsed lymphoma, but is not appropriate for all patients. Conventional salvage chemotherapies have been used with limited efficacy and significant toxicity. Rituximab, gemcitabine and oxaliplatin are active as single agents in relapsed or refractory lymphoma, and have demonstrated synergistic effects in vitro and in vivo. PATIENTS AND METHODS: Forty-six patients with relapsed or refractory B-cell lymphoma received up to eight cycles of R-GemOx (rituximab 375 mg/m(2) on day 1, gemcitabine 1000 mg/m(2) and oxaliplatin 100 mg/m(2) on day 2). The majority (72%) had diffuse large B-cell lymphoma. RESULTS: After four cycles of R-GemOx, the overall response rate was 83% [50% complete response (CR)/unconfirmed CR (CRu)]. High CR/CRu rates were observed in all histological subtypes. In patients who had previously received rituximab, the CR/CRu rate after eight cycles was 65%. The 2-year event-free and overall survival rates (median follow-up of 28 months) were 43% and 66%, respectively. Among responders, the probability of being disease free for 2 years was 62%. Treatment was generally well tolerated. CONCLUSION: R-GemOx shows promising activity with acceptable toxicity in patients with relapsed/refractory B-cell lymphoma who are not eligible for HDT.     

Rituximab, gemcitabine, cisplatin, and dexamethasone in patients with refractory or relapsed aggressive B-cell lymphoma

This study was conducted to evaluate the efficacy and safety of Rituximab, Gemcitabine, Cisplatin, and Dexamethasone (R-GDP) in relapsed or refractory aggressive B-Cell Non-Hodgkin's Lymphoma (NHL). Treatments consisted of rituximab 375?mg/m(2), i.v. on day 1; gemcitabine 1,000?mg/m(2), i.v. on days 1 and 8, dexamethasone 40?mg i.v. on days 1-4, and cisplatin 25?mg/m(2) i.v. on days 1-3, every 21?days. The primary end-points were the overall survival (OS) and progression-free survival (PFS). Secondary endpoints included response rate (ORR; CR) and toxicities. Eligible patients could then proceed to high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) or receive up to six treatment cycles. From January 2005 to December 2010, 50 successive patients at Tianjin cancer hospital lymphoma department were enrolled in this study. All patients were recurrent or refractory aggressive B-cell NHL, including diffuse large B-cell lymphoma (n?=?30) and follicular lymphoma grade 3b (n?=?20). The median follow-up time was 42?months (range, 12-70). After two cycles, the overall response rate was 72.0?%, with a CR/CRu rate of 56?%. The 2-year OS and PFS of all patients were 70.0 and 48.0?%, respectively. Grade III-IV neutropenia and thrombocytopenia occurred in 34 and 40?% of patients, respectively. Twenty-one patients (42?%) proceeded to ASCT. Higher International Prognostic Index and refractory disease were independently associated with worse survival and progression-free survival. R-GDP chemotherapy in patients with refractory or relapsed aggressive B-Cell NHL was effective as a salvage therapy and helpful for HDC/ASCT.     

Phase I trial of iodine-131 tositumomab with high-dose chemotherapy and autologous stem-cell transplantation for relapsed non-Hodgkin's lymphoma.

PURPOSE: To determine the maximum outpatient dose of iodine-131 tositumomab (up to 0.75 Gy) combined with high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem-cell transplantation (ASCT) for the treatment of chemotherapy-resistant relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Twenty-three patients with chemotherapy-refractory or multiply-relapsed B-cell NHL were treated in a phase I trial combining iodine-131 tositumomab (ranging from 0.30 to 0.75 Gy total-body dose [TBD]) with high-dose BEAM followed by ASCT. RESULTS: The complete response rate after transplantation was 57%, and the overall response rate was 65%. Short-term and long-term toxicities were similar to historical control patients treated with BEAM alone. With a median follow-up of 38 months (range, 27 to 60 months), the overall survival (OS) rate was 55%, and the event-free survival (EFS) rate was 39%. CONCLUSION: There were no significant added toxicities apparent with the addition of iodine-131 tositumomab up to a dose of 0.75 Gy TBD to high-dose BEAM chemotherapy followed by ASCT. The EFS and OS were encouraging in this group of chemotherapy-resistant or refractory B-cell NHL patients. A follow-up phase II trial with iodine-131 tositumomab at the dose of 0.75 Gy TBD with BEAM is currently ongoing.     

R-GEMOX方案治疗复发难治B细胞性非霍奇金淋巴瘤的疗效

目的:观察R-GEMOX方案(利妥昔单抗联合吉西他滨、奥沙利铂)挽救性治疗复发、难治B细胞性非霍奇金淋巴瘤(non-Hodgkin's lymphoma,NHL)的近期疗效和毒副反应。方法:回顾性分析20例经正规标准方案治疗复发或难治的B细胞性NHL患者,采用R-GEMOX方案(利妥昔单抗375 mg/m2,第0天;吉西他滨1 000 mg/m2,静脉滴注,第1、8天;奥沙利铂130 mg/m2,静脉滴注,第1天),21～28 d为一个周期,每化疗4个周期后评价疗效,每1个周期化疗后评价毒副反应。结果:20例患者中,完全缓解(complete remission,CR)7例,部分缓解(partial remission,PR)8例,总有效率(CR+PR)为75％。7例具有B类症状的患者,5例症状消失,1例明显改善。毒副反应可耐受。结论:R-GEMOX方案对复发难治B细胞性NHL近期疗效较好,毒副反应小,是一个值得进一步验证的补救性化疗方案。     

Phase I-II Clinical Trial of Oxaliplatin,Fludarabine, Cytarabine,and Rituximab Therapy in Aggressive Relapsed/Refractory Chronic Lymphocytic Leukemia or Richter Syndrome

BackgroundTo improve outcomes of patients with Richter syndrome (RS) and relapsed/refractory chronic lymphocytic leukemia (CLL), we modified the OFAR1 regimen (oxaliplatin and cytarabine doses of the oxaliplatin, fludarabine, cytarabine, and rituximab) for this phase I-II study (OFAR2).Patients and MethodsOFAR2 consisted of oxaliplatin at 30 mg/m² on days 1 to 4, fludarabine at 30 mg/m², cytarabine at 0.5 g/m², rituximab at 375 mg/m² on day 3, and pegfilgrastim at 6 mg on day 6. Fludarabine and cytarabine were given on days 2 and 3 (cohort 1), days 2 to 4 (cohort 2), or days 2 to 5 (cohort 3) every 4 weeks. Phase II followed the “3 + 3” design of phase I.ResultsThe 102 patients (CLL, 67; RS, 35) treated had heavily pretreated high-risk disease. Twelve patients were treated in phase I; cohort 2 was the phase II recommended dose. The most common toxicities were hematologic. Response rates (phase II) were 38.7% for RS (complete response [CR], 6.5%) and 50.8% for relapsed/refractory CLL (CR, 4.6%). The median survival durations were 6.6 (RS) and 20.6 (CLL) months. Among 9 patients who underwent allogeneic stem cell transplantation (SCT) as post-remission therapy, none has died (median follow-up, 15.9 months).ConclusionOFAR2 had significant antileukemic activity in RS and relapsed/refractory CLL. Patients undergoing SCT as post-remission therapy had favorable outcomes.     

Chemoresistance can be overcome with high-dose chemotherapy and autologous stem-cell transplantation for relapsed and refractory Hodgkin lymphoma

BackgroundHigh-dose therapy and autologous stem-cell transplant (HDT/ASCT) is the preferred treatment of chemosensitive relapsed/refractory Hodgkin lymphoma (HL). The role for HDT/ASCT in chemoresistant HL is less well defined. We evaluated long-term outcomes of relapsed/refractory HL patients whose disease was refractory to secondary chemotherapy preceding HDT/ASCT.Patients and methodsAll HL patients who underwent HDT/ASCT in British Columbia for primary progression (PP, defined as progression within 3 months of initial therapy completion) or first relapse (REL1) were reviewed. Patients were grouped based on response to secondary chemotherapy as sensitive (S), resistant (R), and untested/unknown (U).ResultsA total of 256 patients underwent HDT/ASCT for PP (35%) or REL1 (65%) between 1985 and 2011. At median follow-up of 11.7 years, 58% were alive without HL, 36% relapsed; 6% died of transplant-related mortality, 3% secondary malignancies, and 3% unrelated causes. For PP/S, PP/R, and PP/U groups, 10-year FFS were 47%, 31%, and 38%; 10-year OS were 52%, 29%, and 37%, respectively. For REL1/S, REL1/R, and REL1/U groups, 10-year FFS were 64%, 51%, and 81%; 10-year OS were 71%, 59%, and 79%, respectively. In multivariate analysis, resistance to secondary chemotherapy predicted for post-transplant mortality in the PP (P = 0.04) but not REL1 (P = 0.16) groups.ConclusionIn this large uniformly treated cohort of HL patients with long-term follow-up, chemoresistance preceding HDT/ASCT was identified as a poor prognostic factor; however, this factor can be partially overcome by HDT/ASCT, resulting in cure in 30%–50% of patients. HDT/ASCT should therefore be considered in all transplant eligible patients, regardless of responsiveness to salvage chemotherapy.     

IVAC With or Without Rituximab for Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas: Real-World Experience in the Modern Era

IntroductionPart B of the modified Magrath regimen (IVAC) +/- rituximab (R) is recommended as standalone therapy by national guidelines for management of relapsed/refractory Burkitt lymphoma, and is used in other non-Hodgkin lymphomas (NHL). Activity of IVAC in B-cell NHL, particularly with R, and its toxicity remain incompletely described.Patients and MethodsWe reviewed patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 2004 and 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity.ResultsAmong 54 eligible patients (median 2 prior lines of therapy), 76% had diffuse large B-cell lymphoma; 30% had central nervous system involvement at IVAC initiation. Objective response rate was 48%. At median 22-month follow-up, median progression-free and overall survival were 3.1 months and 4.9 months, respectively. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common. Febrile neutropenia occurred in 65% and did not appear to be influenced by use of antimicrobial or granulocyte colony stimulating factor prophylaxis. Mortality was attributed to treatment in 19% of evaluable patients.ConclusionThe clinical efficacy and utility of IVAC +/- R remain unclear. However, its profound hematologic toxicity and life-threatening complications despite prophylactic measures warrant careful consideration of alternatives.     

Prognostic value of the age-adjusted International Prognostic Index in chemosensitive recurrent or refractory non-Hodgkin's lymphomas treated with high-dose BEAM therapy and autologous stem cell transplantation.

High-dose therapy (HDT) is now recommended for patients under 60 years of age with chemosensitive relapsed aggressive non-Hodgkin's lymphoma. However, approximately half of these patients will be cured by HDT. Prognostic factors are needed to predict which patients with chemosensitive lymphoma to second-line therapy could benefit from HDT. We retrospectively investigated the prognostic value of the widely used age-adjusted International Prognostic Index (AA-IPI) calculated at the time of relapse (35 patients) or just before second-line salvage therapy for primary refractory disease (5 patients). The median age was 51 years (range 18-64 years). Thirty-six patients had diffuse large B-cell lymphoma. Salvage cytoreductive therapy before HDT was DHAP/ESHAP (cytarabine, cysplatin, etoposide, steroids) in 17 patients, VIM3-Ara-c/MAMI (high-dose cytarabine, ifosfamide, methyl-gag, amsacrine) in 17 patients, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) or reinforced CHOP in 4 patients, high-dose cyclophosphamide and etoposide in 2 patients. The HDT regimen consisted of BEAM (carmusine, cytarabine, etoposide, melphalan) in all cases. Eleven patients were in partial remission and 29 in complete remission at the time of HDT. Ten patients had an IPI >1, 16 had relapsed early (<6 months after first-line therapy) or disease was refractory to first-line therapy (5 of the 16 patients). The median follow-up was 6.07 years (range 1.24-9.74 years). Overall survival was not statistically different in patients with refractory disease or in those who relapsed early compared with late failures (>6 months after first-line chemotherapy) (P=1), but the AA-IPI >1 was associated with a poor outcome (P=0.03). In conclusion, the AA-IPI could have a prognostic value in patients with chemosensitive recurrent lymphoma treated with BEAM HDT.     

Oxaliplatin‐based chemotherapy (dexamethasone,high‐dose cytarabine,and oxaliplatin) ± rituximab is an effective salvage regimen in patients with relapsed or refractory lymphoma

BACKGROUND:

Patients affected by relapsed or primary refractory lymphomas currently have a poor prognosis and no standard salvage treatment options. This study was carried out to assess the efficacy and safety of a dexamethasone, high‐dose cytarabine, and oxaliplatin as salvage therapy in those patients, replacing cisplatin with oxaliplatin in the standard dexamethasone, cytarabine, and cisplatin scheme.

METHODS:

Seventy patients with relapsed or refractory aggressive non‐Hodgkin or Hodgkin lymphoma were treated from September 2001 to September 2007. The median age of patients was 51 years (range, 19‐75 years). Histological subtypes were: diffuse large B‐cell lymphoma (n = 47) and Hodgkin lymphoma (n = 23). The overall response rate was 73% (51 of 70), with 30 (43%) complete remissions and 21 (30%) partial remissions. Fifty‐two patients were treated with dexamethasone, high‐dose cytarabine, and oxaliplatin as second‐line chemotherapy. Forty‐eight patients were enrolled in an autologous stem cell transplantation program; forty (83%) finally proceeded to high‐dose consolidation and autografting.

RESULTS:

No grade 3 or 4 nonhematological toxicity was demonstrated; in particular, no renal or neurotoxicity was reported. After a median follow‐up period of 21 months (range, 2‐87 months), 22 (31%) patients had died. Probabilities of 2‐year progression‐free survival (PFS) and overall survival (OS) were 44% and 71%, respectively. In the chemosensitive patients, the PFS and OS were 52% and 83%, respectively. The only factor that significantly correlated with better OS was the response to therapy.

CONCLUSIONS:

This study confirms that dexamethasone, high‐dose cytarabine, and oxaliplatin ± rituximab is an effective and feasible outpatient regimen for salvage therapy in patients affected by relapsed or refractory lymphoma. Moreover, the feasibility and efficacy of this scheme as an in vivo chemosensitive test in patients in autotransplantation programs was confirmed. Cancer 2010. © 2010 American Cancer Society.     

GemOX方案治疗老年复发难治性非霍奇金淋巴瘤疗效观察

目的 探讨吉西他滨联合奥沙利铂(GemOX方案)治疗老年复发难治性非霍奇金淋巴瘤(NHL)的疗效和毒副反应.方法全组30例患者均接受GemOX方案化疗:吉西他滨1000 mg/m2,d1.8,静脉滴注;奥沙利铂130 mg/m2,d1,静脉滴注.每21 ～28 d为1个周期,完成2个周期化疗后评价疗效,完成1个周期化疗...     

Stem-cell transplantation in T-cell non-Hodgkin’s lymphomas

BackgroundT-cell lymphomas are a heterogeneous group of non-Hodgkin’s lymphomas (NHLs). With the exception of anaplastic lymphoma kinase protein-positive large-cell lymphoma, standard chemotherapy provides dismal long-term outcomes when compared with NHLs with B-cell immunophenotype.DesignWe review the literature on the role of high-dose chemotherapy (HDT) and autologous stem-cell transplantation (ASCT) in T-cell NHLs both as up-front treatment and in the salvage setting. The role of allogeneic transplantation will also be reviewed.ResultsResults from five prospective, nonrandomized and six retrospective studies evaluating the role of HDT and ASCT in the up-front setting show that patients in first complete or partial remission especially those who present with advanced disease and high prognostic index of peripheral T-cell lymphoma score may benefit from this approach. In the relapsed and/or refractory setting, most series show results that are comparable with those seen in patients with B-cell lymphomas if transplanted with chemosensitive disease. There is limited evidence to suggest that an immune-mediated graft-versus-lymphoma effect may result in long-term disease remissions in some patients after allogeneic transplantation.ConclusionsRandomized studies comparing HDT and ASCT with conventional chemotherapy are needed in T-cell lymphomas.     

Results of a clinical phase I dose-escalation study of cytarabine in combination with fixed-dose vinorelbine, paclitaxel, etoposide and cisplatin for the treatment of relapsed/refractory lymphoma

Management of relapsed lymphoma depends upon the variables of chemosensitive disease and successful stem cell mobilization. The microtubule specific agents, paclitaxel and vinorelbine, have efficacy in relapsed lymphoma and can enhance stem cell mobilization. We performed a phase I dose-escalation study of cytarabine combined with fixed doses of vinorelbine, paclitaxel, etoposide and cisplatin (VTEPA) for patients with relapsed/refractory lymphoma. The regimen consisted of paclitaxel 175 mg/m2 and vinorelbine 30 mg/m2 on day 1; cisplatin 20 mg/m2 and etoposide 100 mg/m2 over 4 h on days 2 - 5. Cytarabine 2 g m/m2 over 4 h, in successive cohorts on 1, 2, or 3 consecutive days: cohort A day 5; cohort B days 4 - 5; and cohort C days 3 - 5. Sixteen patients (Hodgkin's disease, n = 6; non-Hodgkin's lymphoma, n = 10) were enrolled. Fourteen of 16 patients (88%) had refractory and seven patients (44%) had primary refractory disease. Major toxicities included hematologic toxicity, mucositis and infectious complications. Infectious complications (10/16 patients) included neutropenic fever, sepsis and fungal pneumonia. Dose-limiting toxicity was achieved in cohort C, which received three doses of cytarabine. There were 33% partial responses, 27% stable disease and 40% progressive disease following a single cycle of VTEPA. Two of 16 patients suffered treatment-related mortality. Five patients went on to receive autologous (n = 4) or allogeneic transplant (n = 1), and five out of seven patients in this heavily pretreated group who received VTEPA for mobilization of an autologous graft were successfully collected. The recommended dose of cytarabine for further evaluation in a phase II study is 2 g m/m2 for 2 consecutive days in combination with VTEPA. Treatment of subjects with relapsed/refractory lymphoma using VTEPA as second- or third-line salvage therapy produced remissions in some patients and permitted collection of grafts and subsequent autologous transplantation, supporting a planned phase II trial.     

GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤

目的:观察GemOx±R方案治疗复发或难治的侵袭性非霍奇金淋巴瘤（NHL ）的近期疗效和不良反应。方法:经组织学证实的复发或难治的侵袭性29例NHL 患者给予GemOx±R方案:吉西他滨（gemcitabine ）1 000mg/m2,静脉注射,d1、d8;奥沙利铂（oxaliplatin）130mg/m2,静脉注射d1;加/不加利妥昔单抗（rituximab ）375mg/m2,静脉注射,d0。21~28d 为一个周期。每个患者均完成≥2 周期的化疗。结果:29例患者中,总有效率为65.5% ,11例完全缓解（CR）,8 例部分缓解（PR）;B 细胞和T 细胞淋巴瘤患者的有效率分别为68.4% 和60.0% ,差异无统计学意义（P>0.05）;但在B 细胞淋巴瘤中,加用美罗华与否的有效率分别为80.0% 和55.6% ,差异有统计学意义（P=0.043）。 不良反应主要表现为骨髓抑制和胃肠道反应,表现为粒细胞、血小板减少及恶心、呕吐等。结论:GemOx±R方案高效低毒,是针对复发或难治性的侵袭性非霍奇金淋巴瘤安全有效的解救方案。      

利妥昔单抗联合高剂量治疗和自体外周血干细胞移植治疗侵袭性B细胞淋巴瘤的多中心前瞻性研究

目的 探讨在高剂量治疗联合自体外周血干细胞移植的基础上,加用利妥昔单抗治疗侵袭性B细胞淋巴瘤的可行性和疗效.方法 12个癌症研究中心共入组28例侵袭性B细胞淋巴瘤患者,其中22例为新诊断患者,6例为复发患者.每例患者共接受4次利妥昔单抗静脉输注,即在外周血干细胞动员化疗的前1天、动员化疗的第7天、干细胞回输的前1天和回输后的第8天各给予1次,每次375 mg/m2,共1500 mg/m2结果 高剂量治疗后,所有患者均达到完全缓解.中位随访37个月时,全组患者的4年总生存率和无进展生存率分别为75.0%和70.3%,新诊断患者的4年总生存率和无进展生存率均为72.7%.全组患者对利妥昔单抗治疗的耐受性较好,不良反应多为1、2度.结论 在高剂量治疗联合自体造血干细胞移植的基础上加入利妥昔单抗治疗侵袭性B细胞淋巴瘤是可行的,并且可能使患者的生存获益.     

A comprehensive review of lenalidomide therapy for B-cell non-Hodgkin lymphoma

Lenalidomide is an oral non-chemotherapy immunomodulator with direct and indirect effects on non-Hodgkin lymphoma (NHL) cells and with single-agent activity in relapsed/refractory aggressive and indolent B-cell NHL, including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma, and follicular lymphoma. Based on the pivotal phase II MCL-001 trial of lenalidomide in heavily pretreated patients with relapsed/refractory MCL, lenalidomide was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL after failure of two prior therapies, one of which includes bortezomib, at a recommended starting dose of 25 mg on days 1–21 of each 28-day cycle. Lenalidomide enhanced the survival benefit in combination with rituximab in preclinical models, prompting clinical evaluation of the lenalidomide–rituximab (R2) combination. In phase II trials, lenalidomide 20 mg on days 1–21 in combination with different standard-dose rituximab schedules exhibited promising activity in both first-line and relapsed/refractory disease across multiple B-cell NHL subtypes. The feasibility of combining lenalidomide with immunochemotherapy, including R-CHOP and rituximab–bendamustine, has been demonstrated in phase I/II trials. These latter regimens are currently being evaluated in ongoing phase II and III trials. The role of lenalidomide monotherapy and R2 in maintenance therapy is also being examined. Based on available evidence, a comprehensive review of lenalidomide in all treatment phases of B-cell NHL—relapsed/refractory disease, first-line, and maintenance—is presented here.     

GDP方案治疗复发和难治性中高度恶性非霍奇金淋巴瘤

  目的　探讨GDP方案（吉西他滨、顺铂、地塞米松）治疗复发和难治性中高度恶性非霍奇金淋巴瘤（NHL）的疗效和患者不良反应。方法　回顾性分析用GDP方案治疗的32例复发和难治性NHL患者的临床资料,其中复发性NHL 20例,难治性NHL 12例。结果　32例患者均可评价疗效和不良反应,采用GDP方案化疗总的客观有效率59.4 %（19／32）,完全缓解率21.8 %（7／32）,其中B细胞NHL有效率为60.8 %,T细胞NHL有效率为55.5 %。全组总的1年生存率为43.8 %。主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度血小板减少的发生率为31.1 %,Ⅲ～Ⅳ度中性粒细胞减少的发生率为18.6 %,恶心呕吐反应较轻微,经过治疗均可恢复,无治疗相关死亡。结论　GDP方案治疗复发和难治性中高度恶性NHL疗效肯定,不良反应相对较低,值得在更多病例中进一步研究。     

High-dose chemotherapy followed by autologous stem cell transplantation for relapsed or refractory Hodgkin lymphoma: prognostic features and outcomes

Between January 1990 and April 2001, 115 patients received high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) for relapsed or refractory Hodgkin lymphoma (HL). With a median follow-up of 58 months (range, 1 - 175 months), 5-year progression-free survival (PFS) and overall survival (OS) were 46% and 58%, respectively. Twelve patients with primary refractory disease had a 5-year PFS of 41% and OS of 58%, not significantly different from those of the remaining cohort. Early and overall regimen related mortality were 7% and 16%, respectively. Male gender (P = 0.04) and a time to relapse (TTR) < 12 months (P = 0.03) were associated with decreased OS by univariate analysis. In multivariate analysis, TTR < 12 months remained statistically significant (P = 0.04). We have confirmed that HDT and ASCT result in long-term survival for a proportion of patients with relapsed or refractory HL. All patients, including those with primary refractory disease, benefited from HDT and ASCT.     

Salvage chemotherapy with alternating MINE–ESHAP regimen in relapsed or refractory Hodgkin’s lymphoma followed by autologous stem-cell transplantation

BackgroundHigh-dose chemotherapy (HDT) followed by autologous stem-cell transplantation (ASCT) is considered the gold standard in the treatment of patients with relapsed or refractory Hodgkin’s lymphoma (HL). However, the optimal salvage regimen has not yet been established.Patients and methodsWe retrospectively analyzed the efficacy and toxicity of MINE (mesna, ifosfamide, mitoxantrone, and etoposide) alternated with ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) in the treatment of 61 relapsed or refractory HL patients after ABVD-based chemotherapy.ResultsOverall, 25 patients (41%) achieved a complete response (CR), 23 (38%) a partial response (PR), 4 (7%) a stable disease, and 8 (13%) progressed for an overall response rate of 79%. Response to first-line chemotherapy was the most important prognostic factor for response to MINE–ESHAP (P = 0.041). No grade 4 extrahematologic toxic effects or toxic deaths were observed. Adequate peripheral blood stem-cell collection was achieved in 56 of 59 (95%) mobilized patients. Overall survival and event-free survival after HDT and ASCT were significantly higher for patients achieving CR/PR in comparison with those refractory to MINE–ESHAP (46% and 35% versus 74% and 69%, respectively).ConclusionMINE–ESHAP results in a high response rate with acceptable toxicity in patients with HL having failed ABVD-based treatment.     

Phase 2 Study of Daratumumab in Relapsed/Refractory Mantle-Cell Lymphoma,Diffuse Large B-Cell Lymphoma,and Follicular Lymphoma

BackgroundDaratumumab is a CD38 monoclonal antibody approved for treating relapsed/refractory and newly diagnosed multiple myeloma. Preclinical daratumumab studies demonstrated cytotoxic activity and reduced tumor growth in B-cell non-Hodgkin lymphoma (NHL) subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle-cell lymphoma (MCL).Patients and MethodsThis was a phase 2, open-label, multicenter, 2-stage trial. Patients with relapsed/refractory DLBCL, FL, or MCL with ≥ 50% CD38 expression were eligible for stage 1. Daratumumab (16 mg/kg; 28-day cycles) was administered intravenously weekly for 2 cycles, every 2 weeks for 4 cycles, and every 4 weeks thereafter. Overall response rate was the primary end point. Pharmacokinetic and safety were also evaluated. Stage 2 was planned to further assess daratumumab in larger populations of NHL subtypes if futility criteria were not met. The study was registered with ClinicalTrials.gov (NCT02413489).ResultsThe trial screened 138 patients resulting in accrual of 15 patients with DLBCL, 16 with FL, and 5 with MCL. Median CD38 expression across treated patients was 70%. Overall response rate was 6.7%, 12.5%, and not evaluable in DLBCL, FL, and MCL cohorts, respectively. The most common grade 3/4 treatment-emergent adverse event was thrombocytopenia (11.1%), and 4 (11.1%) patients discontinued treatment because of treatment-emergent adverse events. Infusion-related reactions occurred in 72.2% of patients (3 patients with grade 3; no grade 4).ConclusionIn NHL, the safety and pharmacokinetics of daratumumab were consistent with myeloma studies. Screen-fail rates were high, prespecified futility thresholds were met in 2 cohorts, and the study was terminated. Studies in other hematologic malignancies and amyloidosis are ongoing.     

Late Relapses After High-dose Chemotherapy and Autologous Stem Cell Transplantation in Patients With Diffuse Large B-cell Lymphoma in the Rituximab Era

BackgroundThe standard of care for diffuse large B-cell lymphoma (DLBCL) relapsing after front-line therapy is high-dose chemotherapy and autologous stem cell transplantation (ASCT). Evidence has suggested that early relapses (ie, within 1 year) after this approach portends exceptionally poor outcomes. However, data examining relapses > 1 year after ASCT for patients with refractory or relapsed DLBCL are limited, in particular, in the rituximab era. We sought to examine the effect of early (≤ 1 year) and late (> 1 year) relapse after ASCT in a single-institution cohort of patients with relapsed and refractory DLBCL treated with chemoimmunotherapy.Materials and MethodsA retrospective analysis was performed on the data from 85 consecutive patients who had undergone ASCT for biopsy-confirmed relapsed or refractory DLBCL from 2001 to 2010 at the University of Rochester Medical Center. All patients had received rituximab as a part of treatment. Of the 85 patients, 35 developed relapse after ASCT. These 35 patients were divided into 2 groups according to the timing of the relapse (≤ 1 year and > 1 year after ASCT).ResultsThe median follow-up period was 6.4 years. For all patients, the overall survival (OS) from post-ASCT relapse was 5.2 years. For the 27 patients developing relapse at ≤ 1 year after ASCT, the median OS was 0.6 year and progression-free survival was 0.4 year. For the 8 patients developing relapse at > 1 year after ASCT, the median OS was 5.9 years and progression-free survival was 2.9 years.ConclusionPatients with relapsed or refractory DLBCL experiencing relapse > 1 year after ASCT had good outcomes. Despite the relative rarity in incidence, a significant risk of relapse of DLBCL after ASCT remains, suggesting the need for continued monitoring because of the possibility of later progression.