Advances in Treatment of Low-Grade Non-Hodgkin’s Lymphoma (NHL)

Cancer Connect

Advances in Treatment of Low-Grade Non-Hodgkins Lymphoma (NHL): Report from the 2006 Meeting of the American Society of Hematology

C. Dean Buckner, MD, Founding Member, Fred Hutchinson Cancer Research Center

December 9-12, 2006Orlando, FloridaC. Dean Buckner, MD, Founding Member, Fred Hutchinson Cancer Research Center

Introduction

Follicular Lymphoma (FL)

Follicular lymphoma is generally considered to be an incurable disease. However, there has been evidence that recent therapies have improved overall survival. These therapies include more intensive up-front chemotherapy regimens, better maintenance regimes, improved salvage therapies with autologous and allogeneic stem cell transplants and the introduction of monoclonal antibody therapy with Rituxan® (rituximab), Bexxar® (iodine 131 tositumomab) and Zevalin (ibritumomab). Recently, researchers from the M.D. Anderson Cancer Center have documented that overall survival and failure-free survival of patients with stage IV FL significantly improved between 1972 and 2002.[[1]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn1 "_ednref1")

Impact of Rituxan and Rituxan Combination Therapy

Rituxan has undoubtedly been a major factor in the improvement of survival of patients with FL. Researchers affiliated with the E1496 Phase III Trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B have reported that the addition Rituxan to CVP improves survival of patients with FL.[[2]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn2 "_ednref2")

A large EORTC study has shown that Rituxan maintenance improves progression-free and overall survival in patients with relapsed or refractory FL following induction with CHOP or R-CHOP when compared to placebo maintenance.[[3]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn3 "_ednref3") A Canadian study using the data from this EORTC trial (20981) suggests that the addition of Rituxan was cost effective with a gain of 0.8 Quality Adjusted Life Years.[[4]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn4 "_ednref4")

At ASH 2006, researchers from Emory University performed a meta-analysis to determine the benefits of Rituxan plus chemotherapy in producing complete remissions in patients with untreated FL.[[5]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn5 "_ednref5") They concluded that R-CHOP and R-Fludara combinations were superior to Rituxan alone or R-CVP in producing complete remissions. In addition, Rituxan/Fludara combinations produced complete remissions in 85% of patients compared to 65% for R-CHOP.

Researchers from the M.D. Anderson Cancer Center reported that the addition of Rituxan to CHOP provided a high response rate and excellent early survival in a group of good prognosis patients with newly diagnosed FL.[[6]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn6 "_ednref6") This group of 45 patients had a complete response rate of 96%. With a median follow-up of 33 months, they reported a 3-year failure-free survival of 73% with an overall survival of 97%.

Researchers from Germany reported that salvage treatment and maintenance with Rituxan containing regimens was effective in patients with indolent lymphoma who had received prior Rituxan.[[7]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn7 "_ednref7") German researchers also reported that a combination of Treanda® (bendamustin), Novantrone® (mitoxantrone) and Rituxan was effective for the treatment of relapsed and refractory FL patients who had been previously treated with Rituxan.[[8]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn8 "_ednref8") The median age of this group of patients was 67 years with the oldest being 83-years-old. The CR rate for 30 patients with FL was 48%, with 93% achieving a CR or PR. Treanda is a bifunctional agent with both alkylator and purine-like activity that is currently in phase II testing in a variety of diseases. One advantage of Treanda is that it is not cross resistant with other alkylating agents. Treanda has been marketed and used clinically in Germany for many years in patients with NHL, CLL, multiple myeloma, breast cancer and other solid tumors such as lung cancer.

Researchers from M.D. Anderson Cancer Center and other institutions reported the outcomes of a phase I/II trial of pixantrone (BBR 2778) in combination with Fludara, Dexamethasone, and Rituxan in patients with relapsed or refractory low-grade NHL, mostly FL.[[9]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn9 "_ednref9") A previous study has shown that single agent pixantrone produces a high response rate without a decrease in cardiac function in patients with NHL previously treated with anthracyclines.[[10]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn10 "_ednref10") Pixantrone was developed to decrease the cardiotoxicity associated with anthracyclines. One mechanism thought to be responsible for the cardiac toxicity of anthracyclines is through the production of free-radicals. Pixantrone was designed by eliminating two OH molecules while retaining the rest of the mitoxantrone molecule. In the 2006 ASH presentation the overall response rate was 89% with a 70% complete response rate. The median duration of response was 25 months. They reported declines in LVEF in 7 of 28 patients, which was transient in 4. There were no declines >20%. These authors concluded that there were no serious cardiac toxicities in a group of patients where 20 of 28 had received prior anthracyclines.

Velcade® (bortezomib)

Most of the studies of Velcade for treatment of low-grade lymphomas are summarized below in the section on mantle cell lymphoma.

Revlimid® (lenalidomide)

A previous study presented at ASH 2006 showed that Revlimid has significant activity in chronic lymphocytic leukemia (CLL).[[11]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn11 "_ednref11") Researchers involved in a multicenter trial reported the outcomes of 43 patients with relapsed or refractory indolent NHL.[[12]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn12 "_ednref12") The overall response rate was 26% with one CR. The median time to response was 4 cycles of therapy. Toxicities were predominantly hematologic.

Impact of Radio-Immunotherapy

Researchers from several institutions evaluated the efficacy of different front-line regimens in producing CR in patients with FL.[[13]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn13 "_ednref13") These authors evaluated 25 publications that included chemotherapy regimens, chemotherapy plus Rituxan, Fludara, or radio-immunotherapy (Zevalin plus chemotherapy or Fludara) in 2421 patients with FL. They reported that the highest CR rate was associated with Zevalin radio-immunotherapy regimens (79%) compared to 53% for Rituxan-based regimens and 68% for Fludara-based regimens. Patients who achieved a CR were also at lower risk of disease progression. The summary of Zevalin for the treatment of NHL is included in a separate section: Go to: Radio-Immunotherapy with Zevalin®: Update from the 2006 American Society of Hematology Meeting

Autologous Stem Cell Transplantation

A previous randomized study from Europe has documented that high-dose chemotherapy with autologous stem cell support is superior to conventional dose chemotherapy in patients with relapsed FL.[[14]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn14 "_ednref14") The European study presented at EBMT 2004 involved 89 patients with relapsed FL. Patients were randomly allocated to receive 3 courses of conventional chemotherapy, HDC with purging of the graft, or HDC without purging. This study was initiated more than 10 years ago and did not involve the use of newer agents. This study shows that HDC significantly improved PFS and OS compared to conventional chemotherapy.  Since this study was carried out, there have been significant improvements in the treatment of FL and the role of autologous stem cell transplantation needs to be continually assessed.

At ASH 2006, researchers from the Cleveland Clinic reported that prior treatment with Rituxan did not affect the impact of autologous stem cell transplantation.[[15]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn15 "_ednref15") They compared outcomes of 71 patients with no prior Rituxan therapy with 35 patients who had received prior Rituxan. The 3-year OS was approximately 70% in both groups.

Allogeneic Stem Cell Transplantation

The consensus of data suggests that survival of patients with FL is related to complete eradication of molecular evidence of disease. Allogeneic stem cell transplantation is the most effective method of producing molecular remissions in patients with low-grade lymphomas. However, transplant-related mortality is high following conventional myeloablative regimens. Allogeneic stem cell transplants can be performed using reduced-intensity treatment regimens resulting in a lower treatment-related mortality rate and relying on a graft-versus-tumor effect of the graft for the anti-lymphoma effect. However, there has been concern about the long-term effectiveness of this approach, with very little long-term data available.

Researchers from Italy have previously reported that allogeneic stem cell transplantation using a reduced-intensity regimen of Thiotepa, Fludara and Cytoxan results in high rate of complete clinical and molecular remissions in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and FL. The results of this study were presented at the 2005 meeting of the European Group for Blood and Marrow Transplantation in Prague March 20-23, 2005.[[16]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn16 "_ednref16") This clinical trial evaluated a reduced-intensity regimen followed by infusion of allogeneic stem cells in 44 patients with CLL or FL with a median age of 54 years (32-69). Twenty-five percent of these patients had failed an autologous stem cell transplant and 32% were considered chemo-refractory. Twenty-five to these patients had a molecular marker and 15 achieved PCR negativity. The 2-year DFS was 100% for those with PCR negativity compared to 57% for those who were persistently positive. These authors concluded that molecular remissions can be achieved by reduced intensity allogeneic stem cell transplants and that this effect is related to GVHD. They also stated that in the absence of GVHD, the relapse rate was high.

Researchers from Spain reported the results of reduced-intensity allogeneic stem cell transplantation in 35 patients with FL.[[17]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn17 "_ednref17") Half of these patients had failed a prior autologous stem cell transplant. With a median follow-up of 60 months, 20 patients were alive and disease-free. Event-free survival was better in patients with chronic graft-versus host disease (GVHD). However, 12 patients died of transplant-related complications. The median age of this group was 50 years with the oldest being 62 years old.

Researchers from Canada reported the outcomes of 41 patients with FL treated with myeloablative regimens followed by allogeneic stem cell transplants from related or unrelated donors. Four patients had a syngeneic donor. Unrelated donor transplants were conditioned with total body irradiation containing regimens and related donor transplants with busulfan-containing regimens.[[18]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn18 "_ednref18") They reported a 5-year overall survival of 77%. The treatment related mortality was only 12% in this study, which is lower than most studies of reduced-intensity transplants. Only one patient has relapsed and all syngeneic stem cell recipients remain in complete remission. This study is remarkable for the low treatment-related mortality and the low relapse rate. The median age of this group was 45 years with the oldest patient being 57 years of age. The fact that all 4 recipients of identical twin stem cells have not relapsed suggests that a graft-versus-lymphoma effect is not necessary for potential cure of FL if the doses of drugs or irradiation are high enough.

Mantle Cell Lymphoma

Rituxan-Containing Regimens

The impact of Rituxan on outcomes of patients with MCL is less clear than for patients with FL. A previous randomized trial has shown that the addition of Rituxan to CHOP for initial treatment of MCL improves response and time to treatment failure but does not improve survival.[[19]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn19 "_ednref19") However, since there are so many reasonably good salvage therapies, survival is probably not a good endpoint for evaluating initial therapy. It may be more important to achieve molecular remissions in the largest number of patients.

German researchers reported that a combination of Trenda® (bendamustin), Novantrone® (mitoxantrone), and Rituxan was effective for the treatment of relapsed and refractory MCL patients who had been previously treated with Rituxan.[[20]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn20 "_ednref20") This study included 18 patients with MCL. The complete response rate was 42%, and the partial response rate was 50%.

Researchers affiliated with the North Central Cancer Treatment Group reported on a phase 2 study combining Leustat® (cladribine, 2CDA) with Rituxan for the initial treatment of 29 patients with MCL.[[21]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn21 "_ednref21")Leustat is used primarily to treat hairy cell leukemia but has apparently been evaluated as a single agent for the treatment of MCL with significant activity, according to the authors of this study. In this study patients received Neupogen® (filgrastim) or Neulasta® (pegfilgrastim) due to significant neutropenia in the first patients treated. The median age of the patients in this study was 70 years with the oldest being 86-years-old. The complete response rate was 52% with only one of these patients relapsing. Four patients achieved a PR. Most patients received further therapy after failure to respond or progression, but 90% were alive at the time of this report. These authors concluded that Leustat and Rituxan were well tolerated and produced durable remissions in half the patients treated.

Velcade® (bortezomib)

Velcade is the first in a new class of anticancer agents known as proteasome inhibitors and is being evaluated in clinical trials for the treatment of patients with refractory hematologic malignancies and some solid tumors. However, most of the research with this drug has focused on multiple myeloma. Several recent studies have suggested that Velcade has significant activity in patients with aggressive or low-grade NHL. A previous U.S. multicenter trial determined that Velcade was an effective treatment option for patients with relapsed or refractory MCL. The U.S. Food and Drug Administration (FDA) announced in December 2006 the approval of Velcade for patients with MCL who had failed other regimens.

Austrian researchers reported the results of treating 12 patients with relapsed and refractory MCL with a regimen of Velcade, Rituxan and dexamethasone. They reported that 11 patients responded, with 3 achieving a CR, 6 a PR and PR and 2 with stable disease.[[22]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn22 "_ednref22")

Researchers from Ohio State University reported a high response rate for Velcade and Rituxan for the treatment of MCL but an unacceptably high rate of neurotoxicity in 9 patients with MCL or FL.[[23]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn23 "_ednref23") They reported that 5 patients stopped the protocol due to sensory neuropathy, motor neuropathy, constipation, ileus and myositis.

In contrast to the above study, researchers from Memorial Sloan-Kettering Cancer reported that a regimen of weekly or biweekly Velcade in combination with Rituxan, Cytoxan and Prednisone was well tolerated in patients with indolent lymphoma.[[24]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn24 "_ednref24")

Researchers from Germany reported outcomes of a salvage regimen of high-dose cytarabine and Velcade for relapsed MCL.[[25]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn25 "_ednref25") They treated 8 patients with relapsed MCL with a median age of 65 years. The median number or prior regimens was 4. In the 4 patients completing therapy there was one CR and 3 PRs.

Impact of Radioimmunotherapy

Most of the abstracts dealing with radioimmunotherapy involved the study of Zevalin. The summary of Zevalin for the treatment of NHL is included in a separate section: Go to: Radio-Immunotherapy with Zevalin®: Update from the 2006 American Society of Hematology Meeting

Autologous Stem Cell Transplantation

The role of autologous stem cell transplantation for treatment of patients with MCL is continually evolving. There is no question that autologous transplants are more effective than alternative therapies for patients with MCL who have failed first-line therapy. Phase II studies have suggested that early intervention with autologous stem cell transplantation could improve results and possibly cure patients with MCL. However, there have been many additions to available therapies for MCL, including Rituxan, Fludara, and radioactive monoclonal antibodies over the past several years. Thus, the timing of intervention with stem cell transplants has become a major issue in the treatment of low-grade lymphomas, including MCL. French researchers have recently reported that the addition of Rituxan to induction chemotherapy followed by autologous stem cell transplantation improved overall survival of patients with MCL.[[26]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn26 "_ednref26") Following transplantation the CR rate in this study was 77%.

A previous study from the University of Minnesota reported outcomes of 13 patients with MCL treated with an autologous stem cell transplants.[[27]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn27 "_ednref27") The complete remission rate was 83% and at 5 years the overall survival was 42%. There were no transplant-related deaths but the relapse rate was 69%.

Researchers from Northwestern University reported results of autologous stem cell transplants without the use of Rituxan.[[28]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn28 "_ednref28") These researchers treated 25 patients with an intensive induction regimen with a planned autologous or allogeneic stem cell transplant for responders. Only 17 of 25 patients actually received the transplant part of this therapy. The 5-year overall and event-free survivals for the entire group of patients were 49% and 37%, respectively. For the 13 patients who underwent autologous stem cell transplant the overall and event-free survivals were 75% and 54%, respectively.

Italian researchers have previously reported that patients with MCL treated with 4 cycles of therapy, each including Rituxan, with two cycles supported by autologous stem cells results in a high rate of molecular CR.[[29]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn29 "_ednref29") The rationale for this approach is that Rituxan provides in-vivo purging. The original report included 28 previously untreated patients with FL with a median age of 48 years. The current ASH presentation reported the outcomes of a total of 54 newly diagnosed young patients and 19 elderly patients with MCL.[[30]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn30 "_ednref30") Younger patients were subjected to an intensive treatment program involving two cycles of induction with chemotherapy and Rituxan and harvesting of peripheral blood stem cells after high-dose Cytoxan and cytarabine. This was followed by two high-dose regimens which included Alkeran® (melphalan) and Rituxan, followed by peripheral blood stem cell support. Elderly patients received lower doses of Cytoxan, cytarabine and Alkeran than younger patients. They reported that the CR rate after transplantation was 88% in young and 95% in elderly patients. Early treatment-related mortality was 2% in the younger patients, however, there were 6 late toxicity deaths, including a case of lung cancer. There was one treatment-related death in the elderly group. The overall survival at 5 years was 77% with a relapse rate of 29% for the younger group. The overall survival at 5 years was 55% for the older patients.

Researchers from the Netherlands reported preliminary data on HOVOV 45; a phase II study with Rituxan, high-dose cytarabine and autologous stem cell transplant as primary treatment of 83 patients with MCL.[[31]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn31 "_ednref31")The median age was 55 years with the oldest patient being 66 years of age. Newly diagnosed patients with MCL were treated with 3 cycles of R-CHOP, stem cells were collected after high-dose cytarabine and patients received high-dose BEAM chemotherapy followed by infusion of autologous peripheral blood stem cells. The CR rate following R-CHOP was 16%, 34% following cytarabine and 68% following BEAM. For 63 patients completing the two year freedom-from failure rate was 90% with an overall survival of 98%.

Allogeneic Stem cell Transplantation

A previous study from the University of Minnesota reported outcomes of 10 patients with MCL who received an allogeneic stem cell transplant after a myeloablative regimen and 7 patients after reduced-intensity regimens.[[32]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn32 "_ednref32") With a median follow-up as 2.7 years, the 5-year overall survival was 49%. The complete remission rate was 83%. At five years, overall survival was 49% for patients treated with an allogeneic stem cell transplant compared to 42% for similar patients receiving an autologous transplant.

Researchers from M.D. Anderson have previously reported the outcomes of 18 patients with MCL treated with allogeneic stem transplants following a regimen of Cytoxan, Fludara and Rituxan, or Platinol®, Fludara and cytarabine.[[33]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn33 "_ednref33") The median age for patients in this study was 56.5 years with the oldest patient being 64-years-old. Five patients had failed a prior autologous transplant while the remainder had chemosensitive disease. It was reported that no patient died in the first 100 days after transplant. A complete remission was reported in 17 patients with a progression-free survival of 82% with a median follow-up of 26 months. Three patients were given donor lymphocyte infusions following progression. Three patients died: one of infection and graft-versus host disease, one from tumor progression and one from an unrelated cause.

Researchers from Stanford University have reported that the administration of irradiation to all lymphoid tissue combined with anti-thymocyte globulin (ATG) results in a decrease in GVHD without loss of the graft-versus-leukemia (GVL) effect.[[34]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn34 "_ednref34") At ASH 2006 these same researchers reported on a novel method of further decreasing GVHD, i.e. administering post-transplant Rituxan.[[35]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_edn35 "_ednref35") They treated 11 patients with CLL or MCL with their reduced-intensity regimen followed by post-transplant Rituxan. They reported no acute GVHD and only one transient chronic GVHD. Six of the 11 patients achieved a molecular CR.

Summary

There appears to be significant progress in the development of new treatment regimens for patients with indolent lymphomas. Rituxan has made a major impact on the treatment of these diseases, but most patients still relapse. There still appears to be a major role for autologous and allogeneic stem cell transplantation.

References

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[[7]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref7 "_edn7") Dreyling MH, Forstpointner R, Boeck H-P, et al. Combined immuno-chemotherapy followed by rituximab maintenance is an effective salvage treatment after prior rituximab containing therapy: Results of a GLSG-subgroup analysis in patients with relapsed indolent lymphoma. Blood 2006;108:784a, abstract 2769.

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[[9]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref9 "_edn9") Fayad L, Liebmann J, Modiano M, et al. Results of a phse I/II trial of pixantrone (BBR 2778) in combination with fludarabine, dexamethasone and rituximab (FPD-R) in the treatment of patients with relapsed/refractory indolent non-Hodgkins lymphoma (NHL). Blood 2006;108:780a, abstract 2758.

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[[13]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref13 "_edn13") Saville MW, Leonard JP, Hainsworth JD, et al. Role of different frontline regimens in achieving complete response in follicular lymphoma: A meta-analysis of CR rate and its relation to hazard rate for disease progression. Blood 2006;779a, abstract 2754.

[[14]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref14 "_edn14") Schouten H, Qian W, Kvaloy S, et al. High-Dose Therapy Improves Survival in Relapsed NHL; Data From the Randomised CUP Trial. Bone Marrow Transplantation 2004;33, supplement 1:S5, abstract number 0104.

[[15]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref15 "_edn15") Kang TY, Sweetenham JW, Snehal, et al. Prior therapy with rituximab (R) in patients with follicular lymphoma (FL) does not affect relapse-free (RFS) or overall survival (OS) after high dose therapy (HDT) and autologous stem cell transplantation (ASCT). Blood 2006;108:874a, abstract 3069.

[[16]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref16 "_edn16") Farina L, Carrabba R, Milani R, et al. Molecular remission in relapsed/refractory chronic lymphocytic leukemia and follicular lymphoma treated with RIC-allogeneic stem cell transplantation correlates with a better disease-free survival. Bone Marrow Transplantation 2005;35 (supplement 2):S24, abstract number O138. 

[[17]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref17 "_edn17") Caballero M-D, Rodrigo M, Mateos M-V, et al. Long remissions are possible after non myeloablative transplant in patients with follicular non-Hodgkins lymphoma (NHL): Results of two prospective multicenter trials. Blood 2006;108:858a, abstract 3024.

[[18]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref18 "_edn18") Kuruvilla J, Bao Q, Messner E, et al. Favourable overall survival with myeloablative allogeneic stem cell transplantation for follicular lymphoma. Blood 2006;108:852a, abstract 3005.

[[19]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref19 "_edn19") Lenz G, Dreyling M, Hoster E, et al. Immunochemotherapy with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone significantly improves response and time to treatment failue, but not long-term outcome in patients with previously untreated mantle cell lymphoma: results of a prospective randomized trial of the German Low Grade Lymphoma Study Group (GLSG). Journal of Clinical Oncology. 2005;23:1984-1992.

[[20]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref20 "_edn20") Weide R, Hess G, Koeppler H, et al. High anti-lymphoma activity of bendamustine/mitoxantrone/rituximab (BMR) in rituximab pretreated relapsed or refractory indolent lymphoma. A multicenter phase II study of the German Low Grade Lymphoma Study Group (GLSG). Blood2006;108:704a, abstract 2480.

[[21]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref21 "_edn21") Inwards DJ, Hillman DW, Fishkin PA, et al. Phase II study of rituximab and cladribine (2-CDA) in newly diagnosed mantle cell lymphoma (MCL) (NO189). Blood 2006;108777a, abstract 2746.

[[22]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref22 "_edn22") Drach J, Kaufman H, Richelmayer O, Marked activity of bortezomib, rituximab, and dexamethasone in relapsed and refractory mantle cell lymphoma. Blood 2006;108:779a, abstract 2753.

[[23]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref23 "_edn23") Blum KA, Lucas MS, Johnston JS, et al. Excessive neurotoxicity in a phase II trial of combined bortezomib and rituximab in patients with relapsed/refractory mantle cell lymphoma (MCL) and follicular lymphoma (FL) non-Hodgkins lymphoma. Blood 2006;108:784a, abstract 2768.

[[24]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref24 "_edn24") Gerecitano J, Portlock C, Noy A, et al. The schedule dependent combination of bortezomib (Bor) with Rituxan (R), cyclophosphamide © and prednisone (P) produces minimal toxicity, even at relatively high doses of proteasome inhibitor, in patients with relapsed/refractory indolent B-cell lymphoproliferative disorders. Blood 2006;108:781a, abstract 2759.

[[25]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref25 "_edn25") Weigert O, Weidmann E, Mueck R, et al. High-dose cytarabine salvage regimen combined with bortezomib is feasible and highly effective in relapsed mantle cell lymphoma. Blood 2006;108:693a, abstract 2449.

[[26]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref26 "_edn26") Thieblemont C, Antal D, Lacotte-Thierry L, et al. Chemotherapy with rituximab followed by high-dose therapy and autologous stem cell transplantation in patients with mantle cell lymphoma. Cancer. 2005;104:1434-1341.

[[27]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref27 "_edn27") Laudi N, Arora M, Burns L, et al. Efficacy of high-dose therapy and hematopoietic stem cell transplantation for mantle cell lymphoma. American Journal of Hematology. 2006;81:519-424.

[[28]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref28 "_edn28") Evens AM, Winter JN, Hou N, et al. Durable event-free and overall survival (EFS/OS) in mantle cell lymphoma (MCL) without rituximab: Long-term follow-up of a phase II trial with intensive chemotherapy (CTAP/VMAC) followed by autologous hematopoietic stem cell transplant (aHSCT). Blood 2006;108:693a, abstract 2448.

[[29]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref29 "_edn29") Gianni AM, Magni M, Martelli M, et al. Long-Term Remission in Mantle Cell Lymphoma Following High-Dose Sequential Chemotherapy and In Vivo Rituximab-Purged Stem Cell Autografting (R-HDS regimen). Blood 2003;102:749-755.

[[30]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref30 "_edn30") Cortilazzo S, Magni M, Pintimalli M, et al. Frontline high dose sequential chemotherapy with rituximab (R-HDS) induces high rates of complete response and prolongs survival in mantle cell lymphoma (MCL). Blood 2006;108:866a, abstract 3045.

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[[33]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref33 "_edn33") Khouri IF, Lee M-S, Saliba RM, et al. Nonablative Allogeneic Stem-Cell Transplantation for Advanced/Recurrent Mantle-Cell Lymphoma. Journal of Clinical Oncology 2003;21:4407-4412.

[[34]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref34 "_edn34") Lowsky R, Takahashi T, Ping Y, et al. Non-myeloablative conditioning of total lymphoid irradiation (TLI) and anti-thymocyte globulin (ATG) protects against acute GVHD following allogeneic hematopoietic cell transplantation (HCT) but retains anti-tumor activity. Proceedings of the American Society of Hematology. Blood. 2004;104:127a, abstract number 433.

[[35]](http://news.cancerconnect.com/advances-in-treatment-of-low-grade-non-hodgkins-lymphoma-nhl-report-from-the-2006-meeting-of-the-american-society-of-hematology/#_ednref35 "_edn35") Aral S, Sahaf B, Jones C, et al. Rituximab infusion two months after nonmyeloablative transplantations maintains B-cell disease control with minimal GVHD. Blood 2006;108:823a, abstract 2907.

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