Zevalin Radioimmunotherapy Targeted Treatment for non Hodgkin Lymphoma

Zevalin RIT treatment improves the outcome of many groups of NHL patients.

Whjat is Zevalin and How Does it Work?

by Dr. C.D. Buckner M.D., updated 10/1/2018 by Dr., C.H. Weaver M.D.

Zevalin is radioimmunotherapy (RIT). It combines the targeting properties of an antibody with the power of radiation. The antibody targets cells with the CD20 antigen, found on >90% of B-cells,and delivers radiation.

Zevalin RIT is a type of targeted therapy that delivers radiation directly to cancer cells. It combines a monoclonal antibody—a type of protein that recognizes and binds to certain parts of cancer cells—with radioactive material. When the monoclonal antibody binds to the cancer cell, the radiation kills the cell.

RIT is used for the treatment of B-cell non-Hodgkin lymphomas (NHL). RIT is also being evaluated for the treatment of other types of cancer. RIT is given on an outpatient basis as a single treatment, is generally completed in 10 days and avoids many of the side effects of chemotherapy.

Zevalin® (ibritumomab tiuxetan): Zevalin therapy combines the monoclonal antibody Rituxan® (rituximab) with Zevalin, which is comprised of an anti-CD20 monoclonal antibody and Yttrium-90, a radioisotope that delivers the radiation. When injected into the body, Zevalin attaches to a protein (CD20) found only on the surface of B-lymphocytes, such as cancerous B-cells found in many forms of non-Hodgkin’s lymphoma. The radioactivity that is spontaneously emitted targets the B-cell and destroys it. This approach protects healthy tissue.

Zevalin Has Been Used in a Variety to NHL Situations

Advanced Follicular Lymphoma

Researchers conducted a study that included 414 patients with CD20-positive stage III or IV follicular lymphoma who achieved a complete or partial response after first-line induction treatment. Patients were randomly assigned to receive Zevalin or no further treatment.

After a median follow-up of 3.5 years, the results indicated that Zevalin significantly prolonged median progression-free survival (PFS) in all patients, regardless of whether they had achieved a partial or complete response. Median PFS in patients treated with Zevalin was 36.5 months, compared to 13.3 months for patients in the control group. For patients who achieved a partial response after induction treatment, those who received Zevalin had a median PFS of 29.3 months compared to 6.2 months for those in the control group. Among patients who achieved complete response after induction, those who received Zevalin had a median PFS of 53.9 months compared to 29.5 months in the control group. What’s more, 77 percent of patients who experienced a partial response after induction converted to a complete response, which resulted in a final complete response rate of 87 percent.(1)

Sequential R-CHOP plus Zevalin Shows Promise in High-Risk Elderly Patients with Diffuse Large B-Cell Lymphoma

Sequential R-CHOP followed by Zevalin® produces encouraging outcomes in high-risk elderly patients with diffuse large B-cell lymphoma.

Standard treatment for DLBCL typically includes R-CHOP, which refers to treatment with the monoclonal antibody Rituxan® (rituxamab) plus cyclophosphamide/Adriamycin/vincristine/prednisone (CHOP). Although this regimen has led to improved outcomes, there is a group of poor-risk patients who need an alternative treatment strategy.

Researchers conducted a study of 63 evaluable patients with DLBCL and a median age of 75. All patients were untreated and were ineligible for stem cell transplantation. Patients received six cycles of R-CHOP and then those with responding or stable disease received Zevalin 6-9 weeks later.

Following R-CHOP treatment, 50 patients were eligible for Zevalin and 44 were ultimately treated. Zevalin was generally well tolerated and 86 percent of patients experienced a complete response (CR) or unconfirmed complete response (CRu), while 2 percent experienced a partial response. Response improvement (from PR to CR or CRu to CR) occurred in 16 percent of patients. At 42 months, the overall survival for Zevalin treated patients was 83.5 percent and the progression-free survival was 74.5 percent..

Fractionated Zevalin Effective First-Line Treatment for Advanced Follicular Lymphoma

Fractionated radioimmunotherapy treatment with Zevalin® (ibritumomab tiuxetan) is an effective first-line treatment for advanced stage follicular lymphoma and delivers high response rates in patients with high tumor burden.

Some research has indicated that in patients with higher tumor burden, using more than one fraction of RIT increases the overall radiation dose over that of a single fraction of treatment—thereby potentially improving response rates and survival. Researchers conducted an international, mutlitcenter phase II study to evaluate the safety and efficacy of fractionated Zevalin as first-line therapy for follicular lymphoma.

The study included 72 patients (median age 61) with untreated follicular lymphoma and at least one criterion of high tumor burden. Patients were treated with two doses of Zevalin given 8-12 weeks apart. Thirteen patients required pretreatment with Rituxan, 72 received the first Zevalin infusion, and 55 received the second infusion.

The end of treatment response (EOR) was 95.7 percent with CR/CRu of 57.1 percent. Six patients subsequently improved response, resulting in an overall response rate (ORR) of 97.1 percent and CR/Cru of 64.3 percent. After a median follow-up of 1.52 years, the progression-free survival (PFS) was 67 percent and 20 patients had progressed, 12 of whom required further treatment.

Zevalin Plus Nonmyeloablative Allogeneic Transplantation Effective in High-Risk B-Cell NHL

The addition of Zevalin® to nonmyeloablative allogeneic transplantation (NMAT) is safe and produces early responses and prolonged disease control in high-risk patients with B-cell non-Hodgkin’s lymphoma, according to the results of a study published in Blood.

Researchers conducted a study that included 40 patients with persistent, high-risk B-cell NHL. The goal was to evaluate whether the addition of Zevalin to NMAT would deliver safe and effective cytoreduction and provide additional time for the allogeneic graft to take effect. Patients receive Zevalin, fludarabine, and 2 Gy of total body irradiation as conditioning prior to the allogeneic transplant.

The results indicated that 60 percent of patients achieved early responses—14 patients with complete remission or complete remission unconfirmed and 10 with partial response, including 17 of 29 patients (59%) with chemotherapy-resistant disease and 10 patients (59%) with bulk greater than 5 cm. The estimated 30-month survival was 54.1 percent, progression-free survival was 31.1 percent, and nonrelapse mortality was 15.9 percent.

Zevalin Plus BEAM Chemotherapy Superior to BEAM Alone in Aggressive Lymphoma

Standard-dose Zevalin® combined with BEAM high-dose chemotherapy is safe and possibly more effective than BEAM therapy alone as a conditioning regimen for autologous stem cell transplantation (ASCT), according to the results of a study published in Cancer.

High-dose chemotherapy plus autologous stem cell transplantation (ASCT) is standard therapy for refractory/relapsed aggressive lymphoma; however, in the era of frontline regimens that contain Rituxan® it is becoming more challenging to salvage patients in this setting.

To evaluate the safety and efficacy of standard-dose Zevalin combined with high-dose BEAM chemotherapy (Z-BEAM) prior to ASCT, researchers conducted a study that included 43 patients with CD20-positive aggressive lymphoma. Patients were randomized to receive Z-BEAM or BEAM alone.

The results indicated that overall—for all patients—the progression-free survival (PFS) was 48 percent. More specifically, PFS was 59 percent for the Z-BEAM group and 37 percent for the BEAM group. Intermediate-risk patients with one or two risk factors had better PFS with Z-BEAM (69 percent) compared with BEAM (29 percent). Two-year overall survival was 91 percent after Z-BEAM and 62 percent after BEAM.

Dose-Dense R-CHOP plus Zevalin Improves Response in Diffuse Large B-Cell Lymphoma

Dose-dense R-CHOP followed by Zevalin® (converts partial responses to complete responses and maintains durable responses in patients with untreated diffuse large B-cell lymphoma.

Dose-dense R-CHOP refers to treatment that is delivered every 14 days instead of every 21 days. This condensed treatment schedule intensifies the treatment. Researchers conducted a study to evaluate dose-dense R-CHOP followed by consolidation treatment with Zevalin in 20 patients with stages II-IV DLBCL. The median age of patients was 60 (range 33-81) and all patients were previously untreated.

Eighteen patients completed six cycles of R-CHOP and 16 went on to Zevalin consolidation. All 20 patients received 4 or more cycles of R-CHOP alone—and the overall response rate was 100 percent with a 75 percent complete response rate and a 25 percent partial response rate. All four patients who stopped treatment with dose-dense R-CHOP remained in complete response.

Among patients who received Zevalin, three patients converted from partial response to complete response, maintaining an overall response rate of 100 percent and complete response of 90 percent and partial response of 10 percent. The most common grade 3/4 toxicity was neutropenia, which occurred in 50 percent of patients, with no cases of neutropenic fever.

The researchers concluded that consolidation with Zevalin after dose-dense R-CHOP converts partial responses to complete responses and maintains durable responses with acceptable toxicity in patients with untreated DLBCL.

Reference:

  1. Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. Journal of Clinical Oncology. 2008; 26: 5156-5164.
  2. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor–positive breast cancer. Journal of Clinical Oncology. 2006;24(23):3726-34.
  3. O’Connell MJ, Lee M, Lopatin M, et al. Validation of the 12-gene colon cancer recurrence score result in NSABP C-07 as a predictor of recurrence in Stage II and III colon cancer patients treated with 5FU/LV (5FU) and 5FU/LV + oxaliplatin (5FU+Ox). Paper presented at: 48th Annual Meeting of the American Society of Clinical Oncology; June 1-5, 2012; Chicago, IL. Abstract 3512.
  4. Morschhauser F, Radford J, Van Hoof A, et al. Phase III trial of consolidation therapy with yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. Journal of Clinical Oncology. 2008;26(32):5156-64. doi: 10.1200/JCO.2008.17.2015.
  5. Krishnan A, Palmer JM, Tsai NC, et al. Matched-cohort analysis of autologous hematopoietic cell transplantation with radioimmunotherapy versus total body irradiation-based conditioning for poor-risk diffuse large cell lymphoma. Biol Blood Marrow Transplant. 2012; 18: 441-450.
  6. Hamlin PA, Rodriguez MA, Noy A, et al. Final results of a phase II study of sequential R-CHOP and Yttrium-90 Ibritumomab Tiuxetan (RIT) for elderly high risk patients with untreated diffuse large B-cell lymphoma (DLBCL). Blood. 2010; 116(21): Abstract 1793.
  7. Illidge TM, Pettengell R, Bayne M, et al. Fractionated 90Yttrium Ibritumomab Tiuxetan (Zevalin) radioimmunotherapy as an initial therapy of follicular lymphoma: First results from a phase II study in patients requiring treatment according to GELF/BNLI criteria. Blood. 2011; 118(21): Abstract 102.
  8. Gopal AK, Guthrie KA, Rajendran J, et al. Y-ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma. Blood. 2011; 118(4): 1132-1139.
  9. Shimoni A, Avivi I, Rowe JM, et al. A randomized study comparing yttrium-90 ibritumomab tiuxetan (Zevalin) and high-dose BEAM chemotherapy versus BEAM alone as the conditioning regimen before autologous stem cell transplantation in patients with aggressive lymphoma. Cancer. 2012; 118(19): 4706-4714.
  10. Karmali R, Manson A, Bueschel K, et al. Phase II study of 2-weekly CHOP+Rituximab followed by yttrium-90 ibritumomab tiuxetan (Zevalin) in patietns with previously untreated diffuse large B cell lymphoma (DLBCL): Final analysis. Blood. 2010; 116(21): Abstract 3947.

Copyright © 2018 CancerConnect. All Rights Reserved.

Comments