Bruno Royer1, Stéphane Minvielle2, Momar Diouf2, Murielle Roussel2, Lionel Karlin2, Cyrille Hulin2, Bertrand Arnulf2, Margaret Macro2, Sylvie Cailleres2, Annie Brion2, Sabine Brechignac2, Karim Belhadj2, Marie Lorraine Chretien2, Marc Wetterwald2, Carine Chaleteix2, Mourad Tiab2, Xavier Leleu2, Laurent Frenzel2, Laurent Garderet2, Sylvain Choquet2, Jean Gabriel Fuzibet2, Charles Dauriac2, Luc-Matthieu Forneker2, Lotfi Benboubker2, Thierry Facon2, Philippe Moreau2, Hervé Avet-Loiseau2, Jean Pierre Marolleau2. 1. Bruno Royer, Momar Diouf, and Jean Pierre Marolleau, University Hospital, Amiens; Stéphane Minvielle and Philippe Moreau, University Hospital; Stéphane Minvielle, Institut National de la Santé et de la Recherche Médicale U892, Nantes; Murielle Roussel and Hervé Avet-Loiseau, Institute Universitaire du Cancer de Toulouse Oncopole; Hervé Avet-Loiseau, University Hospital, Toulouse; Lionel Karlin, University Hospital, Lyon; Cyrille Hulin, University Hospital, Vandœuvre lès Nancy; Bertrand Arnulf, St Louis University Hospital; Laurent Frenzel, Necker University Hospital; Laurent Garderet, St Antoine University Hospital; Sylvain Choquet, La Pitié University Hospital, Paris; Margaret Macro, University Hospital, Caen; Sylvie Cailleres, General Hospital, Aix en Provence; Annie Brion, University Hospital, Besançon; Sabine Brechignac, University Hospital, Bobigny; Karim Belhadj, University Hospital, Creteil; Marie Lorraine Chretien, University Hospital, Dijon; Marc Wetterwald, General Hospital, Dunkerque; Carine Chaleteix, University Hospital, Clermont-Ferrand; Mourad Tiab, General Hospital, La Roche/Yon; Xavier Leleu, University Hospital, Poitiers; Jean Gabriel Fuzibet, University Department, Nice; Charles Dauriac, University Hospital, Rennes; Luc-Matthieu Forneker, University Hospital, Strasbourg; Lotfi Benboubker, University Hospital, Tours; and Thierry Facon, University Hospital, Lille, France. royer.bruno@chu-amiens.fr. 2. Bruno Royer, Momar Diouf, and Jean Pierre Marolleau, University Hospital, Amiens; Stéphane Minvielle and Philippe Moreau, University Hospital; Stéphane Minvielle, Institut National de la Santé et de la Recherche Médicale U892, Nantes; Murielle Roussel and Hervé Avet-Loiseau, Institute Universitaire du Cancer de Toulouse Oncopole; Hervé Avet-Loiseau, University Hospital, Toulouse; Lionel Karlin, University Hospital, Lyon; Cyrille Hulin, University Hospital, Vandœuvre lès Nancy; Bertrand Arnulf, St Louis University Hospital; Laurent Frenzel, Necker University Hospital; Laurent Garderet, St Antoine University Hospital; Sylvain Choquet, La Pitié University Hospital, Paris; Margaret Macro, University Hospital, Caen; Sylvie Cailleres, General Hospital, Aix en Provence; Annie Brion, University Hospital, Besançon; Sabine Brechignac, University Hospital, Bobigny; Karim Belhadj, University Hospital, Creteil; Marie Lorraine Chretien, University Hospital, Dijon; Marc Wetterwald, General Hospital, Dunkerque; Carine Chaleteix, University Hospital, Clermont-Ferrand; Mourad Tiab, General Hospital, La Roche/Yon; Xavier Leleu, University Hospital, Poitiers; Jean Gabriel Fuzibet, University Department, Nice; Charles Dauriac, University Hospital, Rennes; Luc-Matthieu Forneker, University Hospital, Strasbourg; Lotfi Benboubker, University Hospital, Tours; and Thierry Facon, University Hospital, Lille, France.
Abstract
PURPOSE: Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. PATIENTS AND METHODS: Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). RESULTS: Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). CONCLUSION: In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.
PURPOSE:Primary plasma cell leukemia (pPCL) is a rare and aggressive malignancy with a poor prognosis. With conventional chemotherapy, patients typically die within 1 year. In all but one of the retrospective studies reported to date, bortezomib and lenalidomide seem to improve survival. We conducted a prospective phase II trial in patients with pPCL to assess the efficacy of an alternate regimen that combines standard chemotherapy, a proteasome inhibitor, and high-dose melphalan and autologous stem cell transplantation (HDM/ASCT) followed by either allogeneic transplantation or bortezomib/lenalidomide maintenance. PATIENTS AND METHODS: Patients 70 years old and younger with newly diagnosed pPCL received four alternating cycles of bortezomib, dexamethasone plus doxorubicin or cyclophosphamide. Peripheral blood stem cells were collected from responding patients with < 1% of circulating plasma cells before HDM/ASCT. As consolidation, young patients received a reduced-intensity conditioning allograft, whereas the remaining patients underwent a second HDM/ASCT followed by 1 year of bortezomib, lenalidomide, dexamethasone. The primary end point was progression-free survival (PFS). RESULTS: Forty patients (median age, 57 years; range, 27 to 71 years) were enrolled. The median follow-up was 28.7 months. In the intention-to-treat analysis, the median PFS and overall survival were 15.1 (95% CI, 8.4; -) and 36.3 (95% CI, 25.6; -) months, respectively. The overall response rate to induction was 69%. One patient underwent a syngeneic allograft and 25 HDM/ASCT (16 of whom subsequently received a reduced-intensity conditioning allograft and seven a second ASCT followed by maintenance). CONCLUSION: In this prospective trial in patients with pPCL, we show that bortezomib, dexamethasone plus doxorubicin or cyclophosphamide induction followed by transplantation induces high response rates and appears to significantly improve PFS.
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Authors: R Chakraborty; E Muchtar; S K Kumar; D Jevremovic; F K Buadi; D Dingli; A Dispenzieri; S R Hayman; W J Hogan; P Kapoor; M Q Lacy; N Leung; M A Gertz Journal: Blood Cancer J Date: 2016-12-16 Impact factor: 11.037
Authors: Bharat Nandakumar; Shaji K Kumar; Angela Dispenzieri; Francis K Buadi; David Dingli; Martha Q Lacy; Suzanne R Hayman; Prashant Kapoor; Nelson Leung; Amie Fonder; Miriam Hobbs; Yi Lisa Hwa; Eli Muchtar; Rahma Warsame; Taxiarchis V Kourelis; Stephen Russell; John A Lust; Yi Lin; Mustaqeem Siddiqui; Ronald S Go; Dragan Jevremovic; Robert A Kyle; Morie A Gertz; S Vincent Rajkumar; Wilson I Gonsalves Journal: Mayo Clin Proc Date: 2021-03 Impact factor: 7.616