High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

Morschhauser, Franck; Kraeber-Bodéré, Françoise; Wegener, William A.; Harousseau, Jean‐Luc; Petillon, Marie-Odile; Huglo, D.; Trümper, Lorenz; Meller, J.; Pfreundschuh, Michael; Kirsch, Carl-Martin; Naumann, Ralph; Kropp, J.; Horne, Heather; Teoh, Nick; Gouill, Steven Le; Bodet-Milin, Caroline; Chatal, Jean‐François; Goldenberg, David M.

doi:10.1200/jco.2009.27.7863

Cited by 104 publications

(54 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the single-agent radioimmunotherapy studies using 90 Y-epratuzumab tetraxetan in 64 patients with relapsed/refractory NHL, 98% of patients demonstrated tumor targeting on 111 In imaging. 37 In this study, we also found that outside of clear-cut progression, using a positive PET2 to change therapy is not supported. Fifteen patients were PET2-positive, of whom 8 became PET6-negative and 5 remain progression-free.…”

Section: Org Frommentioning

confidence: 75%

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Micallef

Maurer

Wiseman

et al. 2011

Blood

135

View full text Add to dashboard Cite

Section: Org Frommentioning

confidence: 75%

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Micallef

Maurer

Wiseman

et al. 2011

Blood

135

View full text Add to dashboard Cite

“…Within these targeted therapies, mAbs still remain the best means to bring specifically targeted radionuclides to tumor sites. This technique has demonstrated its efficiency in the treatment of B-cell non-Hodgkin lymphoma by targeting different antigens such as CD20 and CD22, with b-particle emitters such as 90 Y or 131 I (25,26). In the context of MM, the strong expression of syndecan-1 on myeloma tumors makes it a good candidate as a target antigen (27).…”

Section: Discussionmentioning

confidence: 99%

²¹³Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

et al. 2013

View full text Add to dashboard Cite

New multiple myeloma (MM) treatments-such as high-dose melphalan therapy plus autologous stem cell transplantation or regimens incorporating bortezomide, thalidomide, and lenalidomidesubstantially increase the rate of complete response that is associated with longer patient survival. Thus, maintaining the complete response status by improving the minimal residual disease after induction therapy is a key goal for MM management. Here, we address the question of radioimmunotherapy efficacy in MM minimal residual disease treatment in mice with a low tumor burden. a-emitters are particularly well adapted to this approach because the short range of a-particles enables localized irradiation of tumor cells within the bone marrow and a cytotoxic effect on isolated cells due to the high LET (linear energy transfer) of a-particles. The CD138 antigen was used as a target because of its strong expression on myeloma cells in 100% of patients. Method: Intravenous injection of 10 6 5T33 mouse myeloma cells into the Syngeneic mouse strain C57BL/KaLwRij resulted in a rapid invasion of the marrow and limb paralysis, as illustrated by bioluminescence imaging with luciferase-transfected 5T33 cells. Radioimmunotherapy was performed 10 d after 5T33 cell engraftment with an intravenous injection of an antimouse CD138 antibody radiolabeled with 213 Bi at activities of 1.85, 3.7, 7.4, and 11.1 MBq. A blood cell count was performed weekly to monitor hematologic toxicity. The levels of blood Flt3 ligand were also measured to evaluate the radioimmunotherapy-related myelotoxicity. Disease progression was monitored by titrating the monoclonal IgG2b antibody produced by 5T33 cells. Results: The groups treated with 3.7 and 7.4 MBq exhibited a median survival greater than 300 and 227 d, respectively, compared with 45.5 d in the control untreated group. The highest activity (11.1 MBq) showed short-term toxicity whereas the lowest activity (1.85 MBq) gave results similar to those of the controls. With activities of 3.7 and 7.4 MBq, mice exhibited a transient hematologic toxicity whereas only temporary and moderate myelotoxicity was observed with 7.4 MBq. Conclusion: This study demonstrates promising therapeutic efficacy of 213 Bi-labeled antimCD138 for the treatment of residual disease in the case of MM, with only moderate and transient toxicity.

show abstract

“…Epratuzumab (Emab) is a rapidly internalizing (e.g., !50% within 1 hour), humanized anti-CD22 IgG 1 that has been evaluated extensively in lymphoma and leukemia in an unconjugated or conjugated form (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Veltuzumab (Vmab) is a humanized anti-CD20 antibody that is also being studied clinically (23,24) but internalizes slowly (e.g., $10% in 1 hour; refs.…”

Section: Introductionmentioning

confidence: 99%

Epratuzumab–SN-38: A New Antibody–Drug Conjugate for the Therapy of Hematologic Malignancies

Sharkey

Govindan

Cardillo

et al. 2012

Molecular Cancer Therapeutics

Self Cite

View full text Add to dashboard Cite

We previously found that slowly internalizing antibodies conjugated with SN-38 could be used successfully when prepared with a linker that allows approximately 50% of the IgG-bound SN-38 to dissociate in serum every 24 hours. In this study, the efficacy of SN-38 conjugates prepared with epratuzumab (rapidly internalizing) and veltuzumab (slowly internalizing), humanized anti-CD22 and anti-CD20 IgG, respectively, was examined for the treatment of B-cell malignancies. Both antibody-drug conjugates had similar nanomolar activity against a variety of human lymphoma/leukemia cell lines, but slow release of SN-38 compromised potency discrimination in vitro even against an irrelevant conjugate. When SN-38 was stably linked to the anti-CD22 conjugate, its potency was reduced 40-to 55-fold. Therefore, further studies were conducted only with the less stable, slowly dissociating linker. In vivo, similar antitumor activity was found between CD22 and CD20 antibody-drug conjugate in mice-bearing Ramos xenografts, even though Ramos expressed 15-fold more CD20 than CD22, suggesting that the internalization of the epratuzumab-SN-38 conjugate (Emab-SN-38) enhanced its activity. Emab-SN-38 was more efficacious than a nonbinding, irrelevant IgG-SN-38 conjugate in vivo, eliminating a majority of well-established Ramos xenografts at nontoxic doses. In vitro and in vivo studies showed that Emab-SN-38 could be combined with unconjugated veltuzumab for a more effective treatment. Thus, Emab-SN-38 is active in lymphoma and leukemia at doses well below toxic levels and therefore represents a new promising agent with therapeutic potential alone or combined with anti-CD20 antibody therapy.

show abstract

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

Abstract: Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

Cited by 104 publications

References 41 publications

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

²¹³Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Epratuzumab–SN-38: A New Antibody–Drug Conjugate for the Therapy of Hematologic Malignancies

Contact Info

Product

Resources

About

High Rates of Durable Responses With Anti-CD22 Fractionated Radioimmunotherapy: Results of a Multicenter, Phase I/II Study in Non-Hodgkin's Lymphoma

Abstract: Fractionated anti-CD22 radioimmunotherapy provides high total doses of (90)Y, yielding high rates of durable CR/CRus in relapsed/refractory NHL, resulting in 20 mCi/m(2) x 2 weeks as the recommended dose for future studies.

Cited by 104 publications

References 41 publications

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

Epratuzumab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy in patients with previously untreated diffuse large B-cell lymphoma

213Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma

Epratuzumab–SN-38: A New Antibody–Drug Conjugate for the Therapy of Hematologic Malignancies

Contact Info

Product

Resources

About

²¹³Bi Radioimmunotherapy with an Anti-mCD138 Monoclonal Antibody in a Murine Model of Multiple Myeloma