Guenther Koehne - Academia.edu (original) (raw)

Papers by Guenther Koehne

Journal of Clinical Oncology, 2011

The patient was a 60-year-old woman with a history of Langerhans cell histiocytosis who completel... more The patient was a 60-year-old woman with a history of Langerhans cell histiocytosis who completely responded to a 5-month course of cladribine in 2001 to 2002. Seven years later, she presented with a rash on her thighs, fever, and leukocytosis of 180 ϫ 10 3 /uL. Bone marrow biopsy showed acute myelogenous leukemia with a marked increase in blasts. Skin biopsy demonstrated leukemia cutis. The acute myelogenous leukemia was attributed to prior treatment with cladribine. She underwent induction chemotherapy with cytarabine, daunorubicin, and etoposide followed by T cell-depleted allogeneic stem-cell transplantation (SCT) from an 8/10 matched unrelated male donor with busulfan, melphalan, and fludarabine conditioning chemotherapy, with two doses of antithymocyte globulin (ATG). She received four doses of ATG for marrow failure 2 months post transplantation. Patient and donor were cytomegalovirus seropositive.

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Leukemia & lymphoma, Jan 12, 2016

We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusio... more We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet...

Ash Annual Meeting Abstracts, Nov 20, 2009

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Jan 28, 2015

In contrast to the upfront setting in which the role of high dose therapy with autologous hematop... more In contrast to the upfront setting in which the role of high dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a 1(st) remission in patients with multiple myeloma (MM) is well established, the role of high dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN), the American Society of Blood and Marrow Transplantation (ASBMT), and the European Society of Blood and Marrow Transplantation (EBMT) convened a meeting of MM experts to: 1. Summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy; 2. Propose guidelines for the use of salvage HCT in MM; 3. Identify knowledge gaps; 4 Propose a research agenda and 5. Develop a collaborative initiative to move the research agenda forward. After re...

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015

We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadec... more We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadecapeptides (15-mer peptides) spanning the sequence of CMVpp65 for adoptive therapy of 17 allogeneic hematopoietic cell transplant recipients with cytomegalovirus (CMV) viremia or clinical infection persisting despite prolonged treatment with antiviral drugs. All but 3 of the patients had received T cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis with immunosuppressive drugs after transplantation. The CMVpp65-specific T cells (CMVpp65CTLs) generated were oligoclonal and specific for only 1 to 3 epitopes, presented by a limited set of HLA class I or II alleles. T cell infusions were well tolerated without toxicity or GVHD. Of 17 patients treated with transplant donor (n = 16) or third-party (n = 1) CMVpp65CTLs, 15 cleared viremia, including 3 of 5 with overt disease. In responding patients, the CMVpp65CTLs infused consistently proliferated and could be detecte...

Biology of Blood and Marrow Transplantation, 2015

Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high... more Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high-risk leukemias. However, how disease-free survival (DFS) after DCB transplantation (DCBT) compares to that of unrelated donor transplantation (URDT) is not fully established. We analyzed 166 allograft recipients (66 8/8 HLA-matched URDT, 45 7/8 HLA-matched URDT, and 55 DCBT) ages 16 to 60 years with high-risk acute leukemia or chronic myelogenous leukemia (CML). URDT and DCBT recipients were similar except DCBT recipients were more likely to have lower weight and non-European ancestry and to receive intermediate-intensity conditioning. All URDT recipients received a CD34(+) cell-selected (T cell-depleted) graft. Overall, differences between the 3-year transplantation-related mortality were not significant (8/8 URDT, 18%; 7/8 URDT, 39%; and DCBT, 24%; P = .108), whereas the 3-year relapse risk was decreased after DCBT (8/8 URDT, 23%; 7/8 URDT, 20%; and DCBT 9%, P = .037). Three-year DFS was 57% in 8/8 URDT, 41% in 7/8 URDT, and 68% in DCBT recipients (P = .068), and the 3-year DFS in DCBT recipients was higher than that of 7/8 URDT recipients (P = .021). In multivariate analysis in acute leukemia patients, factors adversely associated with DFS were female gender (hazard ratio [HR], 1.68; P = .031), diagnosis of acute lymphoblastic leukemia (HR, 2.09; P = .004), and 7/8 T cell-depleted URDT (HR, 1.91; P = .037). High DFS can be achieved in adults with acute leukemia and CML with low relapse rates after DCBT. Our findings support performing DCBT in adults in preference to HLA-mismatched T cell-depleted URDT and suggest DCBT is a readily available alternative to T cell-depleted 8/8 URDT, especially in patients requiring urgent transplantation.

Infusions of donor peripheral blood T cells can induce durable remissions of Epstein-Barr virus (... more Infusions of donor peripheral blood T cells can induce durable remissions of Epstein-Barr virus (EBV) lymphomas com- plicating marrow grafts, but they contain alloreactive T cells capable of inducing graft-versus-host disease. EBV-specific T-cell lines or clones avoid this problem but require 30 to 40 days of culture to establish. To accelerate the generation of EBV-specific T cells, we tested whether

Biology of Blood and Marrow Transplantation, 2015

Leukemia research, 2005

By activating complement, antitumor monoclonal antibodies coat tumor cells with iC3b. beta-glucan... more By activating complement, antitumor monoclonal antibodies coat tumor cells with iC3b. beta-glucans, naturally occurring glucose polymers, bind to the lectin domain of the leukocyte receptor CR3, prime it for binding to iC3b, and trigger cytotoxicity of iC3b-coated tumor cells. We studied the combination of the complement-activating antibody rituximab with barley-derived (1-->3),(1-->4)-beta-D-glucan (BG) against CD-20 positive lymphoma xenografts in SCID mice. Growth of established subcutaneous non-Hodgkin's lymphoma (NHL) (Daudi and EBV-derived B-NHL) or Hodgkin's disease (Hs445 and RPMI6666) was significantly suppressed in mice treated with a combination of intravenous rituximab and oral BG, when compared to mice treated with rituximab or BG alone. Survival of mice with disseminated lymphoma was significantly increased in the combination group as compared to other treatment groups. No clinical toxicity was observed. The therapeutic efficacy and lack of toxicity of th...

Cancer Immunology Research, 2014

Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in m... more Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in multiple myeloma, exhibits tissue-restricted expression, and is an independent negative prognostic factor for multiple myeloma. We sought to characterize CT7 protein expression in the bone marrow of patients with multiple myeloma undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation (alloTCD-HSCT), and to examine the significance of CT7-specific cellular immune responses. We further aimed to determine CT7-derived immunogenic epitopes and their associated allelic restrictions. CT7 protein expression in neoplastic CD138 þ plasma cells was evaluated by immunohistochemistry in bone marrow biopsies from 10 patients. CT7 was present in 8 of 10 patients. Longitudinal analyses of the 10 patients revealed an association between CT7 expression and prognosis. Longitudinal monitoring of CT7-specific T cells revealed an association between increased frequencies of CT7-specific T cells and reductions in specific myeloma markers. Epitope-specific reactivity to the nonamer FLAMLKNTV was detected by intracellular IFNg assay in peripheral blood (PB) and bone marrow-derived T cells from HLA-A Ã 0201 þ patients. Serial monitoring of PB CT7-specific T-cell frequencies in 4 HLA-A Ã 0201 þ patients by HLA-A Ã 0201-CT7 (1087-1095) tetramer staining revealed an association with disease course. Phenotypic analyses revealed bone marrow enrichment for central memory CT7-specific T cells, while effector memory cells dominated the PB. Together, these findings support the development of immunotherapeutic strategies that aim to enhance CT7-directed immune responses for the treatment of multiple myeloma. Cancer Immunol Res; 2(6); 547-58. Ó2014 AACR.

Blood Cancer Journal, 2012

Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In m... more Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted.

Blood, 2014

Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is saf... more Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623.

Biology of Blood and Marrow Transplantation, 2015

Journal of Clinical Oncology, 2011

The patient was a 60-year-old woman with a history of Langerhans cell histiocytosis who completel... more The patient was a 60-year-old woman with a history of Langerhans cell histiocytosis who completely responded to a 5-month course of cladribine in 2001 to 2002. Seven years later, she presented with a rash on her thighs, fever, and leukocytosis of 180 ϫ 10 3 /uL. Bone marrow biopsy showed acute myelogenous leukemia with a marked increase in blasts. Skin biopsy demonstrated leukemia cutis. The acute myelogenous leukemia was attributed to prior treatment with cladribine. She underwent induction chemotherapy with cytarabine, daunorubicin, and etoposide followed by T cell-depleted allogeneic stem-cell transplantation (SCT) from an 8/10 matched unrelated male donor with busulfan, melphalan, and fludarabine conditioning chemotherapy, with two doses of antithymocyte globulin (ATG). She received four doses of ATG for marrow failure 2 months post transplantation. Patient and donor were cytomegalovirus seropositive.

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Biology of Blood and Marrow Transplantation, 2016

Leukemia & lymphoma, Jan 12, 2016

We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusio... more We conducted a phase II trial investigating the impact of fractionated hematopoietic cell infusions on engraftment kinetics and symptom burden in patients with plasma cell myeloma (PCM) undergoing autologous hematopoietic cell transplant (AHCT). We hypothesized that multiple hematopoietic cell infusions would reduce duration of neutropenia and enhance immune recovery resulting in a better tolerated procedure. Twenty-six patients received high-dose melphalan followed by multiple cell infusions (Days 0, +2, +4, +6) and were compared to PCM patients (N = 77) who received high-dose melphalan and a single infusion (Day 0) (concurrent control group). The primary endpoint was number of days with ANC <500K/mcL. Symptom burden was assessed using the MSK-modified MD Anderson Symptom Inventory. Median duration of neutropenia was similar in study (4 days, range 3-5) and control patients (4 days, range 3-9) (p = 0.654). There was no significant difference in the number of red cell or platelet...

Ash Annual Meeting Abstracts, Nov 20, 2009

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Jan 28, 2015

In contrast to the upfront setting in which the role of high dose therapy with autologous hematop... more In contrast to the upfront setting in which the role of high dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a 1(st) remission in patients with multiple myeloma (MM) is well established, the role of high dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy. The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network (BMT-CTN), the American Society of Blood and Marrow Transplantation (ASBMT), and the European Society of Blood and Marrow Transplantation (EBMT) convened a meeting of MM experts to: 1. Summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy; 2. Propose guidelines for the use of salvage HCT in MM; 3. Identify knowledge gaps; 4 Propose a research agenda and 5. Develop a collaborative initiative to move the research agenda forward. After re...

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2015

We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadec... more We conducted a phase I trial of allogeneic T cells sensitized in vitro against a pool of pentadecapeptides (15-mer peptides) spanning the sequence of CMVpp65 for adoptive therapy of 17 allogeneic hematopoietic cell transplant recipients with cytomegalovirus (CMV) viremia or clinical infection persisting despite prolonged treatment with antiviral drugs. All but 3 of the patients had received T cell-depleted transplants without graft-versus-host disease (GVHD) prophylaxis with immunosuppressive drugs after transplantation. The CMVpp65-specific T cells (CMVpp65CTLs) generated were oligoclonal and specific for only 1 to 3 epitopes, presented by a limited set of HLA class I or II alleles. T cell infusions were well tolerated without toxicity or GVHD. Of 17 patients treated with transplant donor (n = 16) or third-party (n = 1) CMVpp65CTLs, 15 cleared viremia, including 3 of 5 with overt disease. In responding patients, the CMVpp65CTLs infused consistently proliferated and could be detecte...

Biology of Blood and Marrow Transplantation, 2015

Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high... more Double-unit cord blood (DCB) grafts are a rapidly available stem cell source for adults with high-risk leukemias. However, how disease-free survival (DFS) after DCB transplantation (DCBT) compares to that of unrelated donor transplantation (URDT) is not fully established. We analyzed 166 allograft recipients (66 8/8 HLA-matched URDT, 45 7/8 HLA-matched URDT, and 55 DCBT) ages 16 to 60 years with high-risk acute leukemia or chronic myelogenous leukemia (CML). URDT and DCBT recipients were similar except DCBT recipients were more likely to have lower weight and non-European ancestry and to receive intermediate-intensity conditioning. All URDT recipients received a CD34(+) cell-selected (T cell-depleted) graft. Overall, differences between the 3-year transplantation-related mortality were not significant (8/8 URDT, 18%; 7/8 URDT, 39%; and DCBT, 24%; P = .108), whereas the 3-year relapse risk was decreased after DCBT (8/8 URDT, 23%; 7/8 URDT, 20%; and DCBT 9%, P = .037). Three-year DFS was 57% in 8/8 URDT, 41% in 7/8 URDT, and 68% in DCBT recipients (P = .068), and the 3-year DFS in DCBT recipients was higher than that of 7/8 URDT recipients (P = .021). In multivariate analysis in acute leukemia patients, factors adversely associated with DFS were female gender (hazard ratio [HR], 1.68; P = .031), diagnosis of acute lymphoblastic leukemia (HR, 2.09; P = .004), and 7/8 T cell-depleted URDT (HR, 1.91; P = .037). High DFS can be achieved in adults with acute leukemia and CML with low relapse rates after DCBT. Our findings support performing DCBT in adults in preference to HLA-mismatched T cell-depleted URDT and suggest DCBT is a readily available alternative to T cell-depleted 8/8 URDT, especially in patients requiring urgent transplantation.

Infusions of donor peripheral blood T cells can induce durable remissions of Epstein-Barr virus (... more Infusions of donor peripheral blood T cells can induce durable remissions of Epstein-Barr virus (EBV) lymphomas com- plicating marrow grafts, but they contain alloreactive T cells capable of inducing graft-versus-host disease. EBV-specific T-cell lines or clones avoid this problem but require 30 to 40 days of culture to establish. To accelerate the generation of EBV-specific T cells, we tested whether

Biology of Blood and Marrow Transplantation, 2015

Leukemia research, 2005

By activating complement, antitumor monoclonal antibodies coat tumor cells with iC3b. beta-glucan... more By activating complement, antitumor monoclonal antibodies coat tumor cells with iC3b. beta-glucans, naturally occurring glucose polymers, bind to the lectin domain of the leukocyte receptor CR3, prime it for binding to iC3b, and trigger cytotoxicity of iC3b-coated tumor cells. We studied the combination of the complement-activating antibody rituximab with barley-derived (1-->3),(1-->4)-beta-D-glucan (BG) against CD-20 positive lymphoma xenografts in SCID mice. Growth of established subcutaneous non-Hodgkin's lymphoma (NHL) (Daudi and EBV-derived B-NHL) or Hodgkin's disease (Hs445 and RPMI6666) was significantly suppressed in mice treated with a combination of intravenous rituximab and oral BG, when compared to mice treated with rituximab or BG alone. Survival of mice with disseminated lymphoma was significantly increased in the combination group as compared to other treatment groups. No clinical toxicity was observed. The therapeutic efficacy and lack of toxicity of th...

Cancer Immunology Research, 2014

Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in m... more Cancer-testis antigen 7 (CT7) is the most frequently and consistently expressed MAGE antigen in multiple myeloma, exhibits tissue-restricted expression, and is an independent negative prognostic factor for multiple myeloma. We sought to characterize CT7 protein expression in the bone marrow of patients with multiple myeloma undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation (alloTCD-HSCT), and to examine the significance of CT7-specific cellular immune responses. We further aimed to determine CT7-derived immunogenic epitopes and their associated allelic restrictions. CT7 protein expression in neoplastic CD138 þ plasma cells was evaluated by immunohistochemistry in bone marrow biopsies from 10 patients. CT7 was present in 8 of 10 patients. Longitudinal analyses of the 10 patients revealed an association between CT7 expression and prognosis. Longitudinal monitoring of CT7-specific T cells revealed an association between increased frequencies of CT7-specific T cells and reductions in specific myeloma markers. Epitope-specific reactivity to the nonamer FLAMLKNTV was detected by intracellular IFNg assay in peripheral blood (PB) and bone marrow-derived T cells from HLA-A Ã 0201 þ patients. Serial monitoring of PB CT7-specific T-cell frequencies in 4 HLA-A Ã 0201 þ patients by HLA-A Ã 0201-CT7 (1087-1095) tetramer staining revealed an association with disease course. Phenotypic analyses revealed bone marrow enrichment for central memory CT7-specific T cells, while effector memory cells dominated the PB. Together, these findings support the development of immunotherapeutic strategies that aim to enhance CT7-directed immune responses for the treatment of multiple myeloma. Cancer Immunol Res; 2(6); 547-58. Ó2014 AACR.

Blood Cancer Journal, 2012

Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In m... more Light-chain amyloidosis (AL) is a plasma cell dyscrasia closely related to multiple myeloma. In multiple myeloma, the cancer-testis antigens (CTAs) CT7 (MAGE-C1), CT10 (MAGE-C2) and MAGE-A CTAs are expressed in up to 80% of cases. In this study, we investigated the expression and immunogenicity of several CTAs in patients with AL amyloidosis in a total of 38 bone marrow specimens by employing standard immunohistochemistry techniques on paraffin-embedded archival tissues. Plasma samples from 35 patients (27 with matched bone marrow samples) were also analyzed by ELISA for sero reactivity to a group of full-length CTA proteins. CT7 was present in 25/38 (66%) while CT10 was demonstrated in 3/38 and GAGE in 1/38 AL amyloid cases. The expression pattern was mostly focal. There were no significant differences with regard to organ involvement, response to treatment, or prognosis in CTA positive compared to negative cases. None of the specimens showed spontaneous humoral immunity to CT7, but sero reactivity was observed in individual patients to other CTAs. This study identifies CT7 as the prevalent CTA in plasma cells of patients with AL amyloidosis. Further analyses determining the biology of CTAs in AL amyloidosis and their value as potential targets for immunotherapy are warranted.

Blood, 2014

Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is saf... more Standard carfilzomib (20 mg/m(2) cycle 1, 27 mg/m(2) thereafter; 2- to 10-minute infusion) is safe and effective in relapsed or refractory multiple myeloma (R/RMM). We report phase 2 results of carfilzomib 20 mg/m(2) on days 1 to 2 of cycle 1, 56 mg/m(2) thereafter (30-minute infusion), in R/RMM with the option of adding dexamethasone (20 mg) for suboptimal response/progression. Forty-four patients enrolled, all having prior bortezomib and immunomodulatory drugs and a median of 5 prior regimens. Of 42 response-evaluable patients, 23 (55%) achieved at least partial response (PR). Median (95% confidence interval) duration of response, progression-free, and overall survival were 11.7 (6.7-14.7), 4.1 (2.5-11.8), and 20.3 months (6.4-not estimable), respectively. High-risk cytogenetics did not impact outcomes. Treatment was active in bortezomib-refractory subgroups, but these patients tended to have poorer outcomes. Four/10 patients with prior allogeneic transplant achieved at least PR. Of 6 patients who responded, progressed and had dexamethasone added, 4 achieved at least stable disease. The most frequent grade 3/4 adverse events (AEs) possibly related to carfilzomib included lymphopenia (43%), thrombocytopenia (32%), hypertension (25%), pneumonia (18%), and heart failure (11%). Seven patients (16%) discontinued treatment due to AEs. Carfilzomib 56 mg/m(2) ± dexamethasone was tolerable and provided durable responses. This trial was registered at www.clinicaltrials.gov as #NCT01351623.

Biology of Blood and Marrow Transplantation, 2015