GEMOX‐R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large‐cell lymphoma: a phase II study

López, Andrés; Gutiérrez, Antonio; Palacios, Azucena; Blancas, Isabel; Navarrete, Maite; Morey, Miguel; Perelló, Antonia; Alarcón, Jesús; Martínez, J. Larrauri; Rodríguez, José A.

doi:10.1111/j.1600-0609.2007.00996.x

Cited by 97 publications

(78 citation statements)

References 28 publications

(31 reference statements)

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“…In some cases, dramatic responses have been observed; however, in general these agents have shown modest activity in relapsed and refractory DLBCL, with overall response rates ranging from 11 to 47%, CR rates from 1 to 16% and median durations of remission generally in the 2-6 months range (Table 1). [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] For many of these agents, studying specific subtypes of DLBCL (for example, the activated B cell subtype), or cases in which the target of the agent is known to be present, will likely prove to be more effective than simply enrolling all DLBCL cases. Therefore, some subtypes of DLBCL may ultimately prove to be amenable to maintenance therapy post transplant.…”

Section: Modification Of Salvage Therapymentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

Klyuchnikov

Bacher

Kroll

et al. 2013

Bone Marrow Transplant

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Despite overall improvements in outcomes of patients with diffuse large B cell lymphoma (DLBCL), B30-40% of patients develop relapsed or refractory disease. For patients with chemo refractory disease, or recurrent disease following autologous hematopoietic SCT (auto-HCT), the prognosis is poor, with no consensus on the optimal therapy. Currently, owing to the graft vs lymphoma effect, hematopoietic allogeneic hematopoietic cell transplantation (allo-HCT) is the only potentially curative option for such patients. In addition, many patients who are considered today for auto-HCT actually have a low likelihood of benefit. For example, a patient with prior rituximab exposure who relapses within 1 year of diagnosis and has a second-line age-adjusted International Prognosis Index of 2 or 3 at relapse has a o25% chance of being cured by auto-HCT. It is possible that such patients may be better served with an allo-HCT. Unfortunately, in many cases, allo-HCT applicability is limited by patient age, comorbidities, performance status and treatment-related toxicities. Recent attempts to improve the efficacy of auto-HCT, such as incorporating radio-immunotherapy into the conditioning regimen, have not resulted in improved outcomes. However, incorporation of novel agents such as antiprogrammed death-1 antibodies as maintenance therapy after auto-HCT show promise. Allo-HCT in relapsed/refractory DLBCL patients can result in a 30-40% PFS rate at 3 years, in part due to a graft vs DLBCL effect. While reduced-intensity/nonmyeloablative conditioning is increasingly being used, certain patients may benefit from myeloablative conditioning. We present an algorithm intended to discriminate which relapsed and refractory DLBCL patients are most likely to benefit from auto-HCT vs allo-HCT. New approaches, using novel agents that target the molecular heterogeneity in DLBCL, will be an essential component of moving the field forward. Lastly, we propose a prospective registry-based study as the only feasible mechanism to define the optimal position of allo-HCT in the overall treatment strategy for DLBCL. It is hoped that this review will promote the development of prospective multicenter efforts to determine whether such patients do, in fact, benefit from earlier and/or more effective implementation of allo-HCT.

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Section: Modification Of Salvage Therapymentioning

confidence: 99%

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

Klyuchnikov

Bacher

Kroll

et al. 2013

Bone Marrow Transplant

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“…As shown by the studies reported in Table I (12,16,17,25,26,28,29,33,35,(37)(38)(39), the addition of rituximab to salvage chemotherapy improves the response rate, without decreasing the mobilization and collection of PbSC. Moreover, the original reports provide evidence of the lack of significant toxicity due to the addition of rituximab to salvage chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…The toxicity of these regimes is mainly hematological and they generally allow for the adequate collection of PbSC in the majority of patients. The second group is formed by the gemcitabinecontaining regimens, frequently associated with vinorelbine and/or platinum compounds (19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). These regimens produce complete remission rates ranging from 21 to 43%, and are generally less toxic to bone marrow.…”

Section: Discussionmentioning

confidence: 99%

Role of conventional salvage multiple-drug chemotherapy in relapsed and refractory aggressive non-Hodgkin lymphomas

et al. 2010

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Abstract. Autologous stem cell transplantation is the standard care for patients with relapsed or refractory aggressive nonHodgkin lymphomas. Of the patients who are sensitive to second-line chemotherapy, approximately 40-50% are likely to be cured using this approach. The optimal salvage regimen for pre-transplant debulking is controversial and these second-line chemotherapies are particularly important for patients who cannot undergo transplantation for various reasons including age, comorbidity and insufficient stem cell collection. Numerous reports regarding this topic are available. This study evaluated reports published in the last 5 years, focusing on conventional multiple-drug second-line chemotherapies (with or without rituximab), and disregarding single-agent investigational phase-II trials. Results are encouraging, particularly when considering that the more recent and less toxic combinations appear to be equivalent to or even more favourable than previous, more aggressive approaches. Previous results obtained using a combination of mitoxantrone, carboplatin, cytarabine and methylprednisolone, are further updated and included in this study. In conclusion, the most effective conventional chemotherapy currently available for patients with relapsed or refractory nonHodgkin lymphomas obtains complete remission rates of up to 50-70%; the achievement of a complete remission is the most important factor associated with a better outcome. Although the addition of rituximab is beneficial and safe, it is more effective in patients who have previously not been exposed to this monoclonal antibody. The addition of cycles of salvage chemotherapy to those strictly required for mobilization of peripheral blood stem cells ultimately improves the response rate.

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“…While improvements in first-line therapy have resulted in 67% of patients with DLBCL being in a disease-free state 4 years following diagnosis, one-third of patients with DLBCL will have disease that is refractory to initial R-CHOP (<50% decrease in tumor burden) or have a recurrence of their cancer after achieving complete remission (3). Due to the substantial number of patients who have refractory DLBCL, numerous second-line chemotherapy regimens have been developed for the treatment of DLBCL; however, the complete response (CR) rate for these regimens is poor, ranging between 16 and 62% (Table I) (4)(5)(6)(7)(8). Additionally, a number of the second-line regimens for refractory DLBCL have significant side effect profiles (Table I); therefore, novel treatment approaches are required.…”

Section: Introductionmentioning

confidence: 99%

Complete response to azacitidine priming and nab-paclitaxel in non-Hodgkin lymphoma resistant to biochemotherapy

Bowen

Hahn

Butler

et al. 2016

Molecular and Clinical Oncology

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Abstract. The standard of care for first-line therapy in diffuse large B-cell lymphoma (DLBCL) is the rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimen. For patients who fail to respond, have an incomplete response or relapse, numerous effective options exists besides salvage cisplatin-based regimen and autologous stem cell therapy. Even with this approach, the outcome remains very poor for this group of patients. The present case illustrates a 55-year-old woman diagnosed with DLBCL, who experienced an early incomplete response, later progression during treatment with the R-CHOP regimen. The patient received salvage therapy with rituximab, cisplatin and gemcitabine, again with an incomplete response. The patient declined consideration for stem cell therapy. Her disease progressed and she enrolled in the present phase I trial using azacitadine priming and nanoalbumin-bound (nab)-paclitaxel. After three cycles, follow-up positron emission tomography/computed tomography revealed a complete response for the first time since her initial diagnosis and the patient has remained disease-free for >6 years. Azacitadine and nab-paclitaxel combination appeared to be an effective regimen for the treatment of this patient with refractory DLBCL. IntroductionNon-Hodgkin lymphoma (NHL) is the fifth most common cancer type in the USA at 7 cases per 100,000 individuals per year, and is the sixth leading cause of cancer-associated mortality in both men and women (1). Diffuse large B-cell lymphoma (DLBCL) accounts for ~25% of all NHL cases and is an aggressive lymphoma with patients only having months to live without treatment (2). The first-line chemotherapy for the treatment of DLBCL is rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP). While improvements in first-line therapy have resulted in 67% of patients with DLBCL being in a disease-free state 4 years following diagnosis, one-third of patients with DLBCL will have disease that is refractory to initial R-CHOP (<50% decrease in tumor burden) or have a recurrence of their cancer after achieving complete remission (3). Due to the substantial number of patients who have refractory DLBCL, numerous second-line chemotherapy regimens have been developed for the treatment of DLBCL; however, the complete response (CR) rate for these regimens is poor, ranging between 16 and 62% (Table I) (4-8). Additionally, a number of the second-line regimens for refractory DLBCL have significant side effect profiles (Table I); therefore, novel treatment approaches are required. The present study reported a case of refractory DLBCL treated with a novel chemotherapeutic regimen, azacitidine priming followed by nanoparticle albumin-bound (nab)-paclitaxel, that may have promise as a second-line treatment for refractory DLBCL. Case reportA 55-year-old Caucasian female initially presented to the Mitchell Cancer Institute (Mobile, AL, USA) in September 2006 with B-symptoms of night sweats, a 40 pound weight loss and abdominal pain. Initial compu...

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GEMOX‐R regimen is a highly effective salvage regimen in patients with refractory/relapsing diffuse large‐cell lymphoma: a phase II study

Cited by 97 publications

References 28 publications

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

Allogeneic hematopoietic cell transplantation for diffuse large B cell lymphoma: who, when and how?

Role of conventional salvage multiple-drug chemotherapy in relapsed and refractory aggressive non-Hodgkin lymphomas

Complete response to azacitidine priming and nab-paclitaxel in non-Hodgkin lymphoma resistant to biochemotherapy

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