166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials

Giralt, Sergío; Bensinger, William I.; Goodman, Mark; Podoloff, Donald A.; Eary, Janet F.; Wendt, Richard; Alexanian, Raymond; Weber, Donna M.; Maloney, David G.; Holmberg, Leona; Rajandran, Joseph; Breitz, Hazel B.; Ghalie, Richard; Champlin, Richard

doi:10.1182/blood-2002-10-3250

Cited by 108 publications

(63 citation statements)

References 26 publications

(21 reference statements)

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“…In phase I/II trials, increasing doses of 166 Ho-DOTMP were given, along with high-dose melphalan, followed by autologous stem-cell transplant. [39] A complete response rate of 38% was observed, with a median overall survival in excess of 48 months. Sammarium-153, another high-energy isotope, was linked to another tetraphosphonate chelate (EDTMP) and studied in 18 patients with multiple myeloma, who received melphalan 200 mg/m 2 following the isotope.…”

Section: Where Do We Go With Allografts?mentioning

confidence: 97%

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Bensinger

2007

Best Practice & Research Clinical Haematology

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Despite significant improvements in survival for multiple myeloma patients through autologous stem-cell transplantation (SCT) and the introduction of novel drugs, the disease remains incurable for all but a small fraction of patients. Only allogeneic SCT is potentially curative, due in part to a graft-versus-myeloma effect. High transplant-related mortality with allogeneic SCT is currently the major limitation to wider use of this potentially curative modality. Mortality can be reduced through the use of lower-intensity conditioning regimens which allow engraftment of allogeneic stem cells, but this comes at a cost of higher rates of disease progression and relapse. Promising studies to improve outcomes of allogeneic transplants include the use of more intensive nonmyeloablative conditioning regimens, tandem transplants, peripheral blood cells, graft engineering to improve the graft-versus-myeloma activity while reducing graft-versus-host disease (GVHD), post-transplant maintenance, and targeted conditioning therapies such as bone-seeking radioisotopes. Keywords multiple myeloma; allogeneic stem-cell transplantationThe treatment of multiple myeloma has dramatically improved in the last 10 years. Highdose therapy followed by autologous stem-cell support has emerged as a promising means for increasing remission rates and improving survival. As such, autologous stem-cell transplantation has become the standard of care for many patients with multiple myeloma. In addition, insights into the biology and genetics of myeloma cells have resulted in the rapid introduction of new drugs with unique mechanisms of action. These drugs -which include thalidomide, lenalidomide and bortezomib -have shown significant activity in multiple myeloma, and when these new agents are combined with more traditional drugs, the response and complete remission rates are as high as responses achieved with autologous stem-cell transplantation. [1,2] Despite these advances, long-term survival after treatment with stem-cell transplantation or the newly developed drugs is rare, and disease recurs in virtually all patients.Stem-cell transplantation from allogeneic donors may be curative for 10-20% of patients with chemotherapy-resistant, refractory hematologic malignancies, and for up to 80% of . E-mail address: wbensing@fhcrc.org. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. patients who are transplanted in remission. Much of the high response and curative potential of allografts is attributed to a 'graft-versus-tumor' effect. In patients with multiple myeloma this effect has been well documented...

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Section: Where Do We Go With Allografts?mentioning

confidence: 97%

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Bensinger

2007

Best Practice & Research Clinical Haematology

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“…Phase I/II trials of radiophosphonates (containing 153 Sm or 166 Ho, respectively) added to mel200 conditioning showed no change in outcomes with little toxicity, though renal failure due to thrombotic microangiopathy was seen with doses >30Gy of the 166 Holmium conjugate (Giralt et al, 2003;Dispenzieri et al, 2010). The combination of bortezomib with the 153 Samarium conjugate demonstrated promising synergy in mice and merits further clinical investigation (Goel et al, 2006).…”

Section: Augmentation With Radiotherapy/radiopharmaceuticalsmentioning

confidence: 99%

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Maybury

Cook

Pratt

et al. 2016

Biology of Blood and Marrow Transplantation

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SummaryConsolidation with high dose chemotherapy and autologous stem cell transplantation (ASCT) is the standard of care for transplant eligible patients with multiple myeloma, based on randomised trials showing improved progression free survival with autologous transplantation following combination chemotherapy induction. These trials were performed before novel agents were introduced, and subsequently combinations of immunomodulatory drugs (IMiDs) and proteasome inhibitors as induction therapy have significantly improved rates and depth of response. Ongoing randomised trials are testing whether conventional autologous transplantation continues to improve responses following novel agent induction. While these results are awaited, it is important to review strategies for improving outcomes following ASCT. Conditioning prior to ASCT with higher doses of melphalan, and combinations of melphalan with other agents, including radiopharmaceuticals have been explored. Tandem ASCT, consolidation and maintenance therapy following ASCT have been investigated in phase III trials. Experimental cellular therapies using ex vivo primed dendritic cells , ex vivo expanded autologous lymphocytes, KIR-mismatched allogeneic NK cells, and genetically modified T cells are also in phase I trials to augment ASCT. This review summarises these strategies and highlights the importance of exploring strategies to augment ASCT even in the era of novel agent induction.

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“…Complete remission rates have also been observed by others in MM after 166 Ho-DOTMP, high-dose melphalan, and PBSCT. 9 Unfortunately, this patient progressed again with meningeal disease, suggesting that the CNS is a sanctuary site for tumor cells even after high-dose chemo-and radiotherapy.…”

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confidence: 99%

“…8 Treatment with 186 Re-HEDP aiming at myeloablation has not been reported, although 186 Re leads to more homogeneous irradiation of the bone marrow. Considering renal and bladder toxicity, 9 the longer half-life is an advantage, although the resulting longer interval until SCT can be performed might be a drawback. No severe nonhematological side effects were observed and contin- uous bladder irrigation was successful in preventing hemorrhagic cystitis.…”

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Complete remission after myeloablation with bone-seeking 186Re-HEDP and high-dose melphalan followed by autologous stem cell transplantation in a patient with chemorefractory multiple myeloma

Wiesmann

Einsele

Kanz

et al. 2005

Bone Marrow Transplant

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166Ho-DOTMP plus melphalan followed by peripheral blood stem cell transplantation in patients with multiple myeloma: results of two phase 1/2 trials

Cited by 108 publications

References 26 publications

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Is there still a role for allogeneic stem-cell transplantation in multiple myeloma?

Augmenting Autologous Stem Cell Transplantation to Improve Outcomes in Myeloma

Complete remission after myeloablation with bone-seeking 186Re-HEDP and high-dose melphalan followed by autologous stem cell transplantation in a patient with chemorefractory multiple myeloma

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