Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

We present the long-term results of 18 chemotherapy relapsed indolent (N = 12) or transformed (N = 6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, (131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.     

Multicenter phase II study of bendamustine for relapsed or refractory indolent B‐cell non‐Hodgkin lymphoma and mantle cell lymphoma

Bendamustine is a unique cytotoxic agent that has demonstrated efficacy in the treatment of indolent B‐cell non‐Hodgkin lymphomas (B‐NHLs). In this multicenter phase II trial, the efficacy and safety of bendamustine were evaluated in Japanese patients with relapsed or refractory indolent B‐NHL or mantle‐cell lymphoma (MCL). Patients received bendamustine (120 mg/m²) on days 1–2 of a 21‐day cycle, for up to six cycles. The primary endpoint was the overall response rate (ORR) as assessed by an extramural committee according to International Workshop Response Criteria (IWRC). Secondary endpoints included complete response (CR) rate, ORR according to Revised Response Criteria (revised RC), progression‐free survival (PFS), and safety. Fifty‐eight patients with indolent B‐NHL and 11 with MCL were enrolled. By IWRC, bendamustine produced an ORR of 91% (95% confidence interval [CI], 82–97%; 90% and 100% in patients with indolent B‐NHL and MCL, respectively), with a CR rate of 67% (95% CI, 54–78%). ORR and CR rates according to revised RC were 93% (95% CI, 84–98%) and 57% (95% CI, 44–68%), respectively. After a median follow‐up of 12.6 months, median PFS had not been reached. Estimated PFS rates at 1 year were 70% and 90% among indolent B‐NHL and MCL patients, respectively. Bendamustine was generally well tolerated. Reversible myelosuppression, including grade 3/4 leukopenia (65%) and neutropenia (72%), was the most clinically significant toxicity observed. Common non‐hematologic toxicities included mild gastrointestinal events and fatigue. These results demonstrate the high efficacy and tolerability of single‐agent bendamustine in relapsed patients with indolent B‐NHL or MCL histologies. (ClinicalTrials.gov ID: NCT00612183). (Cancer Sci 2010;)     

Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

Background

Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.

Methods

Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (¹³¹I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine ¹³¹I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.

Results

6.956-19.425GBq of ¹³¹I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.

Conclusion

Myeloablative RIT with ¹³¹I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.     

Report of a European consensus workshop to develop recommendations for the optimal use of (90)Y-ibritumomab tiuxetan (Zevalin) in lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) comprises a group of related haematological malignancies, predominantly of B-cell origin, which have been described as indolent or aggressive according to their clinical course. Standard treatment for indolent NHL consists of conventional chemotherapy, but, although long-term remissions may occur, most patients will die of their disease. Radioimmunotherapy (RIT) is a novel modality for treating indolent NHL, using monoclonal antibodies to target tumour cells with systemic, low-dose radiation. (90)Y-Ibritumomab tiuxetan (Zevalin); Schering AG, Berlin, Germany), the first RIT approved for use in relapsed/refractory indolent NHL, comprises the murine anti-CD20 monoclonal antibody ibritumomab, covalently linked to the high-energy beta-emitter, yttrium-90, by the chelator, tiuxetan. MATERIALS AND METHODS: A multidisciplinary consensus workshop of European clinicians who had taken part in clinical trials of (90)Y-ibritumomab tiuxetan was convened to develop recommendations for the clinical preparation and administration of (90)Y-ibritumomab tiuxetan in Europe. The workshop was held in anticipation of European Medicines Agency approval of this agent, which was gained in 2004 for adult patients with rituximab-relapsed or refractory CD20(+) follicular B-cell NHL. RESULTS AND CONCLUSIONS: This article summarises the consensus recommendations developed for hemato-oncologists.     

Bendamustine produces durable responses with an acceptable safety profile in patients with rituximab-refractory indolent non-Hodgkin lymphoma

BackgroundAlthough initially responsive to therapy, indolent non-Hodgkin lymphomas (NHLs) are generally incurable. Therefore, active and tolerable treatments for patients with relapsed or refractory disease are needed. Bendamustine, a mechlorethamine alkylator with novel mechanisms of action, is approved in the United States for rituximab-refractory indolent B-cell NHL.Patients and MethodsData from 2 North American multicenter studies with similar design, enrollment, and response criteria were pooled to evaluate safety and durability of response. Bendamustine was administered at 120 mg/m² days 1 and 2 every 21 days for 6-8 cycles. Endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and safety.ResultsThe studies enrolled 161 patients with a median of 2 previous chemotherapy regimens. Histologies included follicular (68%), small lymphocytic (20%), marginal zone (11%), and lymphoplasmacytic (1%) lymphoma. Sixty patients (34.1%) were refractory to their last chemotherapy, 53 (30.1%) were alkylating agent refractory. Overall response rate was 76% with 23% complete remissions (CRs) and unconfirmed CR (CRu). The median follow-up was 25.3 months (range, 24-27.8 months) and DOR was 10 months (range, 8.3-14 months). At 1 and 2 years, 45% and 23% of responders continued to respond. Among 127 patients previously treated with alkylators, ORR was 88% (28% CR/CRu) in responsive and 59% (12% CR/CRu) in refractory patients. Fifty opportunistic infections were reported in 48 patients. Second malignances occurred in 9 patients (5.6%; 5 myelodysplastic syndromes, 2 acute myelogenous leukemia, 1 chronic myelomonocytic leukemia, and 1 squamous cell carcinoma).ConclusionBendamustine induces durable responses with acceptable long-term safety in rituximab-refractory indolent NHL.     

Radioimmunotherapy in non-Hodgkin's lymphoma: focus on 90Y-ibritumomab tiuxetan (Zevalin)

Radioimmunotherapy (RIT), in which a radionuclide conjugated to an antibody directed towards a tumor associated antigen (the radioimmunoconjugate) is administered in a therapeutic regimen, represents a significant addition to the treatment of non-Hodgkin's lymphoma (NHL). RIT offers several advantages for this heterogenous disease, foremost being the ability to kill tumor cells adjacent to cells to which the radioimmunoconjugate is bound (the cross-fire effect). Thus, RIT is cytotoxic to tumor cells that may be inaccessible to the antibody, or do not express the target antigen in sufficient quantities for antibody binding. The radioimmunoconjugate 90Y-ibritumomab tiuxetan is directed against the B-cell antigen, CD20. Phase II and III clinical trials with this agent report overall response rates of 74% to 83% (complete response rates 15% to 51%) in patients with relapsed or refractory, indolent or transformed NHL, including patients refractory to rituximab. Median durations of response range up to 13.9 months. A variety of RIT approaches are under investigation to improve outcomes in patients with NHL, including the use of radioimmunoconjugates combined with chemotherapy, and myeloablative therapeutic strategies.     

Clinical experience of bendamustine treatment for non-Hodgkin lymphoma and chronic lymphocytic leukemia in Spain

Bendamustine is a alkylating agent with a purine-like benzamidazole ring currently approved in Europe for indolent non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma. Our aim was to analyze retrospectively the efficacy and toxicity of bendamustine in NHL and CLL in Spain in the bendamustine Compassionate Use Program. Patients with relapsed/refractory NHL or CLL were eligible. Any regimen containing bendamustine was eligible. 109 patients were included from 22 institutions. Forty-nine patients had indolent NHL, 18 aggressive NHL and 42 CLL, being 44 patients (40%) refractory to previous treatment. 63% of patients had adverse events grade 3-4, mainly hematological. Overall response rate (ORR) was 66%, complete responses 30%. ORR observed in refractory patients was 45%. The median progression-free survival (PFS) was 13 months. Outcome was influenced by histology, number of previous treatments, resistance to previous chemotherapy and type of response achieved with bendamustine. Alone or in combination, bendamustine shows a meaningful clinical antitumor activity in patients with relapsed or refractory NHL or CLL, with an acceptable toxicity profile.     

惰性淋巴瘤治疗进展

惰性淋巴瘤诊断时多为晚期,一般认为常规化疗不能治愈。随着新的化疗药物以及免疫靶向治疗抗CD20单克隆抗体利妥昔的广泛用于惰性淋巴瘤治疗,研究结果显示了利妥昔单药治疗复发/难治性惰性淋巴瘤的突出疗效;利妥昔单药或与化疗联合用于惰性淋巴瘤的一线诱导治疗以及维持治疗的显著效果,并可获得分子学缓解,使得惰性淋巴瘤的有效率和长期生存得到了明显改善。     

New developments in immunotherapy for non-Hodgkin’s lymphoma

The clinical development of immunotherapy with rituximab (chimeric anti-CD20 monoclonal antibody) has markedly affected the treatment approach for patients with B-cell non-Hodgkin’s lymphoma (NHL). Rituximab was initially evaluated in relapsed indolent lymphoma and has substantial activity in this setting both alone and in combination with chemotherapy. Ongoing efforts in indolent NHL are seeking to optimize the dose and schedule of rituximab through ‘maintenance’ strategies exploring chemotherapyrituximab combinations and the use of other biologic agents or antibodies that may enhance activity when employed together with rituximab. Other studies in indolent NHL suggest that radiolabeled anti-CD20 antibodies (such as I-131 tositumomab and Y-90 ibritumomab tiuxetan) may be useful in relapsed and refractory disease and have potential utility as part of initial treatment as well. In diffuse large B-cell lymphoma, the addition of rituximab to CHOP chemotherapy can improve survival, though benefits are more limited in mantle cell lymphoma. Further studies of unlabeled and radiolabeled immunotherapies are ongoing in order to optimize their use for maximal clinical benefit.     

131I–Tositumomab in lymphoma

Radioimmunoconjugates are radioisotope-bound monoclonal antibodies that target radiation specifically to sites of lymphoma involvement. Initial studies of ¹³¹I–tositumomab in non-Hodgkin lymphoma (nhl) have suggested benefit in patients with relapsed or refractory indolent disease. However, the routine adoption of this agent is tempered by concerns about associated toxicities and unclear long-term benefit. Based on a comprehensive search for studies on ¹³¹I–tositumomab use in lymphoma, this systematic review summarizes and evaluates the evidence on

• the benefits and risks of this novel therapy,
• the predictors for response and toxicity, and
• the role of dosimetry and imaging studies before treatment.

We identified 18 trials investigating the use of ¹³¹I–tositumomab for the treatment of adult patients with nhl. In trials of patients with relapsed or refractory indolent nhl, overall response rates ranged from 67% to 83%. In patients with follicular nhl refractory to the monoclonal antibody rituximab, response rates remained high (65%–72%). However, in rituximab-naïve patients with relapsed or refractory indolent or transformed nhl, improvements in time to progression or survival have not been clearly established. ¹³¹I–Tositumomab is an active agent in relapsed and refractory non-Hodgkin lymphoma that should be considered in selected patients.     

Traditional treatment approaches in B-cell non-Hodgkin's lymphoma

Current treatment of non-Hodgkin's lymphoma (NHL) is based, to a large extent, on stratification of patients into groups based on disease subtype (indolent or aggressive) and stage, and still relies heavily on traditional approaches based on external beam irradiation and alkylating agent-based chemotherapy. Here, we describe risk-based patient management, and the benefits made possible by different treatments. Early-stage localized disease is effectively managed with irradiation and/or chemotherapy; chlorambucil in the case of indolent disease and CHOP-based therapy in the case of aggressive disease. Progress is underway in two crucial areas of the treatment of advanced-stage low-grade NHL: development of first-line therapies to improve the number and quality of complete responses (CRs), and investigation of novel radioimmunotherapy or monoclonal antibody/chemotherapy combination regimens to combat relapsed and refractory disease. New chemotherapy approaches, such as fludarabine phosphate-based combination chemotherapy for low-grade advanced-stage NHL have improved the number and quality of remissions in chemotherapy-na?ve and relapsed patients, but it remains to be seen what the long-term impact on survival may be. Monoclonal antibody based therapies including radioimmunotherapy, is emerging as a highly effective tool for the treatment of NHL, and shows synergy with fludarabine phosphate-based chemotherapy, though its optimal role has yet to be determined. At present, for patients with untreated disseminated disease; recurrent disease; or high-grade disease in the presence of poor risk factors; alternative treatment strategies are needed.     

Salvage therapy with ProMACE-MOPP followed by intensive chemoradiotherapy and autologous bone marrow transplantation for patients with non-Hodgkin's lymphoma who failed to respond to first-line CHOP.

PURPOSE: We used alternative chemotherapy immediately followed in early-response patients by high-dose chemoradiotherapy and autologous bone marrow transplantation (ABMT) to treat patients with non-Hodgkin's lymphoma (NHL) who had failed to respond to first-line chemotherapy. PATIENTS AND METHODS: Thirty-one patients with NHL of intermediate- or high-grade malignancy who had failed to respond to first-line cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy were treated. Seventeen patients had primary refractory disease and 14 had relapsed from first complete response (CR). The treatment consisted of prednisone, methotrexate, doxorubicin, cyclophosphamide, etoposide, mechlorethamine, vincristine, and procarbazine (ProMACE-MOPP) salvage chemotherapy, followed, in case of responsive disease (at least partial response [PR]), by high-dose cyclophosphamide and total-body irradiation (TBI) with ABMT. RESULTS: Twenty-eight of 31 (90%) patients achieved PR (23 patients) or CR (five patients) with ProMACE-MOPP, and three failed to respond. Seventeen of 28 (61%) patients who responded underwent the ABMT procedure, which resulted in CR in 14 patients (82%); three failed to respond. Eleven responsive patients were not transplanted because of residual bone marrow infiltration (five patients), patient refusal (four patients), and ProMACE-MOPP-related mortality (two patients). To date, nine patients are alive and in CR, seven with a median follow-up of 41 months (range, 17 to 84 months). Referring to the original CHOP treatment, five of 17 (29%) patients with primary refractory disease remain free of disease at a median of 36 months after ABMT, and four of 14 (29%) patients in first relapse remain free of disease at a median of 33 months after ABMT. One patient died of AMBT-related toxicity. CONCLUSION: ProMACE-MOPP salvage chemotherapy produces a high early-response rate in patients who fail to respond to first-line CHOP, and more than half of the responding patients can be scheduled to receive ABMT, resulting in disease-free survival (DFS) at 3 years in 50% of the transplanted patients and in 25% of the original number of patients intended to receive this treatment.     

Repeated radioimmunotherapy with 131I-rituximab for patients with low-grade and aggressive relapsed or refractory B cell non-Hodgkin lymphoma

Purpose

A single treatment of ¹³¹I-rituximab in patients with B cell non-Hodgkin lymphoma (NHL) showed a modest rate of response (29 %) in a relatively short duration (median 2.9 months). On the basis of this result, we investigated whether repeated treatment with ¹³¹I-rituximab could improve the response.

Patients and methods

Thirty-one patients with relapsed or refractory B cell NHL received unlabeled rituximab (70 mg) immediately prior to the administration of a therapeutic dose of ¹³¹I-rituximab. The tumor response was evaluated 1 month later by contrast-enhanced ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography. Radioimmunotherapy (RIT) was repeated at 4-week intervals.

Results

A total of 87 cycles of RIT were administered. Repeated RIT yielded twofold increases in response rate (68 %) and in median response duration (8.6 months). This protocol also induced a favorable response in patients with an aggressive histology compared to that induced by a single treatment (50 vs. 9 %, respectively, p = 0.063). The toxicities were principally hematologic with grade 4 thrombocytopenia occurring in 12 % and neutropenia occurring in 17 % of the 85 assessable cycles.

Conclusions

Compared to a single treatment, repeated RIT with ¹³¹I-rituximab increased the response rate and duration for patients with relapsed or refractory B cell NHL, including those with an aggressive histology.     

Comparison of ICE (ifosfamide-carboplatin-etoposide) versus DHAP (cytosine arabinoside-cisplatin-dexamethasone) as salvage chemotherapy in patients with relapsed or refractory lymphoma

Background: High dose chemotherapy with autologous stem cell transplantation is currently the treatment of choice for relapsed or refractory lymphoma patients. However, its applicability is mostly restricted to patients responding to salvage chemotherapy. Optimal salvage regimen for these patients is unclear. In this study, our aim was to compare the efficacy and toxicity profiles of DHAP (cytosine arabinoside, cisplatin and dexamethasone) and ICE (ifosfamide, carboplatin and etoposide) regimens in the salvage treatment of relapsed and refractory lymphoma. Patients and Methods: In this retrospective analysis, 53 patients with primary refractory or relapsed Hodgkin's disease (HD) (n = 13) or non-Hodgkin lymphoma (NHL) (n = 40) who received ICE or DHAP salvage regimen were included. Results: Of 53 patients, 21 (39,6%) were female and the median age was 43 years. A total of 73 courses of ICE and 59 courses of DHAP were administered. Response could be evaluated in 49 patients (36 NHL and 13 HD). Of 49 patients, 11 (22.5%) achieved complete remission (CR) and 17 (35%) achieved partial remission (PR), leading to an overall response rate (ORR: CR + PR) of 57.5%. In the evaluable ICE group (n = 22) rates of CR, PR, and ORR were 27%, 41% and 68% and in the DHAP group (n = 27) rates of CR, PR, and ORR were 18%, 30% and 48% (p = 0.24, for ORR). Toxicity with both regimens was within acceptable limits. The major grade III-IV toxicities for both groups were hematological (neutopenia and thrombocytopenia). The main non-hematological toxicity was renal and observed in 8 patients. Conclusion: Although the toxicity profiles of both ICE and DHAP regimens were similar in the treatment of patients with relapsed or refractory HD or NHL, ICE seems to have higher rates of response than DHAP regimen does.     

Prognostic value of positron emission tomography (PET) with fluorine-18 fluorodeoxyglucose ([18F]FDG) after first-line chemotherapy in non-Hodgkin's lymphoma: is [18F]FDG-PET a valid alternative to conventional diagnostic methods?

PURPOSE: A complete remission (CR) after first-line therapy is associated with longer progression-free survival (PFS). However, defining CR is not always easy because of the presence of residual masses. Metabolic imaging with fluorine-18 fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) offers the ability to differentiate between viable and fibrotic inactive tissue. In this study, we evaluated the value of PET in detecting residual disease and, hence, predicting relapse after first-line treatment in patients with non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Ninety-three patients with histologically proven NHL, who underwent a whole-body [18F]FDG-PET study after completion of first-line chemotherapy and who had follow-up of at least 1 year, were included. Persistence or absence of residual disease on PET was related to PFS using Kaplan-Meier survival analysis. RESULTS: Sixty-seven patients showed a normal PET scan after first-line chemotherapy; 56 of 67 remained in CR, with a median follow-up of 653 days. Nine of these patients with a residual mass considered as unconfirmed CR received additional radiotherapy. Only 11 of 67 patients relapsed (median PFS, 404 days). Persistent abnormal [18F]FDG uptake was seen in 26 patients, and all of them relapsed (median PFS, 73 days). Because standard restaging also suggested residual disease, 12 patients received immediate secondary treatment. In 14 of 26 patients, only PET predicted persistent disease. From these patients, relapse was proven either by biopsy (n = 8) or by progressive disease on computed tomography or magnetic resonance imaging (n = 6). CONCLUSION: Persistent abnormal [18F]FDG uptake after first-line chemotherapy in NHL is highly predictive for residual or recurrent disease. In relapsing patients, PFS was significantly shorter after a positive scan than after a negative scan.     

Comparison on therapeutic effects of RFT and RCTVP regimen in the treatment of patients with indolent B-cell lymphoma in China

To compare the efficacy and safety of RFT (retuximab, fludarabine, pirarubicin) with RCTVP (retuximab, cyclophophamide, pirarubicin, vindesine and prednisone) in 248 indolent B-cell non-Hodgkin's lymphoma (NHL) patients. Two hundred and forty-eight patients with indolent B-cell NHL were treated with combined chemotherapy, including RFT and RCTVP, from January 2002 to December 2010 in Tianjin Cancer Hospital. The rate of response, toxicity and long-term survival for the two regimens were analyzed retrospectively. For the previously untreated patients, overall response rate for RFT arm and RCTVP arm was 71.7 and 70.6%, and complete response rate was 47.5 and 54.9%, respectively (P?>?0.05). For the refractory and relapsed patients, overall response (OR) rate and complete response (CR) rate were significantly improved in the RFT arm versus the RCTVP arm (P?相似文献   

Therapy-related myelodysplastic syndrome and acute myeloid leukemia following initial treatment with chemotherapy plus radioimmunotherapy for indolent non-Hodgkin lymphoma

Patients with indolent non-Hodgkin lymphoma (I-NHL) often receive multiple courses of cytotoxic chemotherapy over several years. Radioimmunotherapy (RIT) has become an important part of treatment for relapsed patients and tositumomab/lodine I-131 tositumomab is a promising regimen currently being incorporated into first-line therapy. While treatment-related myelodysplasia (tMDS) and acute myeloid leukemia (tAML) are well-known, poor-prognosis complications of conventional chemotherapy and radiation therapy, they have not been previously observed as a consequence of initial treatment with RIT-based regimens. We describe four patients with tMDS/tAML who received a sequential chemotherapy and tositumomab/lodine I-131 tositumomab program as their initial and only lymphoma treatment. Our findings suggest that the potential risk of these important complications must be considered in the development of this novel therapeutic strategy in the first-line setting.     

Radioimmunotherapy as a therapeutic option for Non-Hodgkin's lymphoma

Radioimmunotherapy (RIT) represents a relatively new antibody-based radiopharmaceutical treatment for patients with various kinds of tumors. Although the field has a long history of preclinical and clinical investigations using many different agents, to date, only 2 of these immunologically targeted radiopharmaceuticals have been cleared for commercial sale. Both of these agents ((90)Y-ibritumomab tiuxetan or "Zevalin" [Biogen-Idec, Boston, MA] and (131)I-tositumomab or "Bexxar" [GlaxoSmithKline Research, Triangle Park, NC]) are directed against the CD20 surface antigen found on normal mature B cells and greater than 95% of B-cell non-Hodgkin lymphoma (NHL). Both compounds produce similar impressive clinical outcomes (approximately 20%-40% complete response rates and 60%-80% overall response rates for patients with indolent B-cell NHL). Current protocol-based investigations of anti-CD20 RIT relate to new clinical uses and new CD20(+) targets.     

Ifosfamide, epirubicin, etoposide (IEV) and autologous peripheral blood progenitor cell transplant: a feasible and effective salvage treatment for lymphoid malignancies

The IEV schedule consisted of epirubicin 100 mg/m2 on day 1, etoposide 150 mg/m2 on days 1-3, and ifosfamide 2.5 g/m2 on days 1-3. Patients who proceeded to haematopoietic stem cell transplants (HDTs) received conditioning therapy with BEAM [for the Hodgkin's Lymphoma (HL) and non-Hodgkin's Lymphoma (NHL) groups], or melphalan 100 mg/m2 and mitoxantrone [for the multiple myeloma (MM) patients]. The study consisted of 65 patients with a median age of 53 years: 27 had aggressive NHL, 20 had HL, 7 had indolent NHL, and 11 had MM. Fifty-five patients received IEV for a disease that was refractory to conventional induction regimens, or that was in first or second relapse; 4 patients were treated with IEV while in complete response (CR) after chemotherapy in order to mobilise peripheral blood stem cells (PBSCs). Ninety percent of patients with HL responded to IEV, and 85% achieved CR. Both aggressive and indolent NHLs were less responsive (ORR 50 and 33%, respectively; CRR 41 and 16.5%, respectively). MM patients displayed an intermediate responsiveness (ORR 50% and CRR 30%). IEV was well tolerated in most patients. No life- threatening infections were recorded. PBSC mobilisation was successful in 37 out of 39 patients (95%) and led to the collection of a median of 16, 12, and 13.7 x 10(6) CD34+ cells/kg in patients with HL, NHL, and MM, respectively. All 37 patients underwent an autologous stem cell transplant following a 1 to 2 month interval after the end of IEV. Two patients were submitted to an allogeneic transplant. The median overall survival rate in HL, aggressive NHL, and indolent NHL is 32 (5-60), 16 (2-46), and 14 (4-42) months, respectively. Median EFS is 31 (5-60), 7 (2-46), and 7.5 (4-42) months, respectively. In conclusion, our study confirms that IEV +/- HDT is a well-tolerated and effective salvage treatment for lymphoid malignancies, and that IEV acts as an excellent stem cell mobiliser.     

Use of rituximab in patients with follicular lymphoma

Advanced stage symptomatic follicular non-Hodgkin's lymphoma (NHL) is rarely, if ever, curable with conventional chemotherapy. Patients classically experience a pattern of remission and relapse, eventually dying of their disease. Data from a number of large-scale randomised phase III trials, both as first-line therapy and in relapsed/refractory patients, comparing rituximab plus chemotherapy with chemotherapy alone indicate that the addition of rituximab to a number of different chemotherapy regimens increases response rates and progression-free survival (PFS), without significantly increasing toxicity. Moreover, in four trials, three in first-line and one in relapsed disease, a significant overall survival benefit has been observed for rituximab combination therapy. These data indicate that patients with follicular NHL who require therapy should now receive rituximab plus chemotherapy as first-line treatment. Additionally, a strong case remains for offering rituximab-based therapy to patients with relapsed disease who have not previously received it, and in those who have previously responded well to this agent. Rituximab maintenance therapy has also been shown to significantly prolong PFS after rituximab in combination with chemotherapy in patients with relapsed disease and in newly diagnosed patients who have not received rituximab during induction, and the benefit of maintenance after immunochemotherapy in relapsed patients may yet be mirrored by ongoing studies in the first-line setting. This overview considers the most recently published clinical trials of rituximab and their potential effect on clinical practice in the treatment of follicular NHL.