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Koichi Akashi - One of the best experts on this subject based on the ideXlab platform.

  • higher incidence of Injection Site Reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen
    European Journal of Haematology, 2013
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Koichi Akashi
    Abstract:

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that Injections of scBor should be rotated among eight different Sites on the abdomen and thigh. However, detailed information about Injection Site Reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor Injections in ten patients, whereas grade 2 ISRs occurred following seven Injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh Injections but only in 1 of 93 (1.1%) abdominal Injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next Injection even if it occurs.

  • Injection Site Reaction after subcutaneous administration of bortezomib in japanese patients with multiple myeloma
    International Journal of Hematology, 2012
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Yoshikiyo Ito, Koichi Akashi
    Abstract:

    in patients treated with subcutaneous Bor (sBor) was nearly equal to that in patients treated with intravenous Bor (ivBor), although the incidence and severity of PN in patients treated with sBor was lower than those in patients treated with ivBor [2‐4]. The most common Injection Site Reaction was erythema, however, only four patients (3 %) developed an Injection Site Reaction of grade 3 or more, necessitating a reduction in Bor dose in two (1 %) patients [3]. The Injection Site Reactions in the other two patients treated with sBor were severe, although detailed information regarding the clinical courses following these Reactions was not provided [3]. According to a classification of skin symptoms, Bor is classified as an irritant, as it causes extravasation of cytotoxic agents [5]. Further studies that focus on Injection Site Reaction of sBor, particularly in Japanese patients, are required. The present study retrospectively analyzed Injection Site Reactions in 19 Japanese patients with newly diagnosed (n = 9) or relapsed (n = 10) MM, and who were treated with sBor at a concentration of 2.5 mg/ml (3.0 mg Bor reconstituted with 1.2 ml normal saline), as described previously [3], between April 2011 and June 2012. We injected bortezomib to eight different Sites in the right and left abdomen, upper and lower quadrant, or right and left thigh, proximal and distal Sites of each patient in turn, as described previously [3]. These patients were treated with weekly BD (Bor 1.3 mg/m 2 on day 1, 8, 15, 22, and

Tomohiko Kamimura - One of the best experts on this subject based on the ideXlab platform.

  • higher incidence of Injection Site Reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen
    European Journal of Haematology, 2013
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Koichi Akashi
    Abstract:

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that Injections of scBor should be rotated among eight different Sites on the abdomen and thigh. However, detailed information about Injection Site Reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor Injections in ten patients, whereas grade 2 ISRs occurred following seven Injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh Injections but only in 1 of 93 (1.1%) abdominal Injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next Injection even if it occurs.

  • Injection Site Reaction after subcutaneous administration of bortezomib in japanese patients with multiple myeloma
    International Journal of Hematology, 2012
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Yoshikiyo Ito, Koichi Akashi
    Abstract:

    in patients treated with subcutaneous Bor (sBor) was nearly equal to that in patients treated with intravenous Bor (ivBor), although the incidence and severity of PN in patients treated with sBor was lower than those in patients treated with ivBor [2‐4]. The most common Injection Site Reaction was erythema, however, only four patients (3 %) developed an Injection Site Reaction of grade 3 or more, necessitating a reduction in Bor dose in two (1 %) patients [3]. The Injection Site Reactions in the other two patients treated with sBor were severe, although detailed information regarding the clinical courses following these Reactions was not provided [3]. According to a classification of skin symptoms, Bor is classified as an irritant, as it causes extravasation of cytotoxic agents [5]. Further studies that focus on Injection Site Reaction of sBor, particularly in Japanese patients, are required. The present study retrospectively analyzed Injection Site Reactions in 19 Japanese patients with newly diagnosed (n = 9) or relapsed (n = 10) MM, and who were treated with sBor at a concentration of 2.5 mg/ml (3.0 mg Bor reconstituted with 1.2 ml normal saline), as described previously [3], between April 2011 and June 2012. We injected bortezomib to eight different Sites in the right and left abdomen, upper and lower quadrant, or right and left thigh, proximal and distal Sites of each patient in turn, as described previously [3]. These patients were treated with weekly BD (Bor 1.3 mg/m 2 on day 1, 8, 15, 22, and

Paul J Duic - One of the best experts on this subject based on the ideXlab platform.

  • imct 08react long term survival from a randomized phase ii study of rindopepimut cdx 110 plus bevacizumab in relapsed glioblastoma
    Neuro-oncology, 2015
    Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Daniela A Bota, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J Duic
    Abstract:

    BACKGROUND: EGFRvIII, a constitutively active EGFR deletion driver mutation, is associated with poor long-term survival in glioblastoma (GB). The investigational vaccine rindopepimut consists of an EGFRvIII-specific peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies in newly diagnosed, resected, EGFRvIII+ GB demonstrated encouraging progression-free survival (PFS), overall survival (OS) and safety. METHODS: In the Phase II “ReACT” study, 73 bevacizumab (BV)-naive pts in 1st or 2nd relapse with EGFRvIII+ GB were randomized 1:1 to BV plus double-blinded Injection of rindopepimut or control (KLH). Endpoints: 6-month PFS (PFS6; primary; target α = 0.2 by 1-sided chi-square test), objective response rate (ORR), PFS, OS and safety. RESULTS: Primary rindopepimut toxicity is Grade 1-2 Injection Site Reaction. For rindopepimut + BV vs. KLH + BV (per centralized review; RANO criteria): PFS6 = 28% (10/36) vs. 16% (6/37) (p = 0.116); ORR = 30% (9/30) vs. 18% (6/34). Cessation of steroids > 2 months: 44% (8/18) vs 21% (4/19), >6 months: 33% (6/18) vs. 0. Median (95% CI) OS = 11.6 (10.0, 16.2) vs. 9.3 (7.1, 11.3) months (HR = 0.57 [0.33, 0.98], p = 0.039). 9 vs 6 pts remain in follow-up; 6 vs. 2 are progression-free. OS analyses adjusted for various prognostic factors consistently favor rindopepimut. Rindopepimut induced robust anti-EGFRvIII titers (1:12,800-1:6,553,600) in 80% of pts. Antibodies, predominantly IgG1 isotype, mediate killing of EGFRvIII+ tumor cells through ADCC and CDCC in vitro. Within the rindopepimut arm, peak titer (≥1:12,800 at any time) and rapid titer generation (≥1:12,800 by Day 57) were associated with prolonged OS (HR = 0.16, p = <0.0001 and HR = 0.59, p = 0.182, respectively). Evaluation of humoral response quality, HLA typing vs. outcome, and survival follow-up continue. In an additional cohort of BV-exposed pts (n = 53), four pts experienced objective tumor response. CONCLUSIONS: Rindopepimut induces potent EGFRvIII-specific immune response and tumor regression, and appears to significantly prolong survival when administered with BV, in pts with relapsed GB.

  • it 30react a phase ii study of rindopepimut vaccine cdx 110 plus bevacizumab in relapsed glioblastoma
    Neuro-oncology, 2014
    Co-Authors: David A Reardon, Annick Desjardins, David Tran, Karen Fink, Louis B Nabors, Rimas V Lukas, Lynn S Ashby, James M Schuster, Paul J Duic, Lynn Aneiro
    Abstract:

    BACKGROUND: EGFRvIII, a constitutively active tumorigenic EGFR deletion mutation, is linked to poor long-term survival. The investigational vaccine rindopepimut consists of the unique EGFRvIII peptide sequence conjugated to keyhole limpet hemocyanin (KLH), delivered intradermally with GM-CSF. Three phase II studies of rindopepimut in newly diagnosed, resected, EGFRvIII+ glioblastoma have shown encouraging PFS and OS. Bevacizumab (BV), an agent with activity in glioblastoma, may augment EGFRvIII-specific immune response and antitumor activity through inhibition of VEGF and its immunosuppressive properties. METHODS: “ReACT” is a Phase II study of rindopepimut plus BV in patients with 1st or 2nd relapse of EGFRvIII+ glioblastoma. BV-naive pts (Group 1; n = 70) are randomized 1:1 to BV plus double-blinded Injection of either rindopepimut or control (KLH). BV-refractory patients (progression within 2 months of BV; Group 2/2C, n = 98) receive BV plus open-label rindopepimut. RESULTS: 234/700 (33%) screened patients are EGFRvIII+. 115 patients (Group 1 = 72, Group 2/2C = 43) are enrolled. Primary toxicity is Grade 1-2 Injection Site Reaction. In group 1, for rindopepimut + BV vs. KLH + BV, objective response rate (ORR; investigator-assessed, RANO criteria) is 23% (6/26) vs 12% (3/25) [35% vs. 20% including responses observed at a single time point (“unconfirmed”)]. In Group 2/2C (evaluable n = 30), one unconfirmed PR and one sustained PR (patient continues treatment at 15 months) occurred. Two additional patients had pre-study progression >2 months after BV; one maintained a CR for 11.1 months (peak anti-EGFRvIII titer = 1:3,276,800), while the second experienced an unconfirmed CR. Median peak rindopepimut-induced anti-EGFRvIII humoral response is 1:25,600 [range <1:100-1:6,553,600]). Rapid titer generation was associated with prolonged OS (Group 2: p = 0.01). CONCLUSIONS: Rindopepimut + BV has induced potent EGFRvIII-specific immune response and tumor regression in immunosuppressed recurrent glioblastoma patients naive or refractory to BV. Full response, PFS and OS data are expected to further define the potential clinical benefit of the combination in relapsed glioblastoma.

Toshihiro Miyamoto - One of the best experts on this subject based on the ideXlab platform.

  • higher incidence of Injection Site Reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen
    European Journal of Haematology, 2013
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Koichi Akashi
    Abstract:

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that Injections of scBor should be rotated among eight different Sites on the abdomen and thigh. However, detailed information about Injection Site Reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor Injections in ten patients, whereas grade 2 ISRs occurred following seven Injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh Injections but only in 1 of 93 (1.1%) abdominal Injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next Injection even if it occurs.

  • Injection Site Reaction after subcutaneous administration of bortezomib in japanese patients with multiple myeloma
    International Journal of Hematology, 2012
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Yoshikiyo Ito, Koichi Akashi
    Abstract:

    in patients treated with subcutaneous Bor (sBor) was nearly equal to that in patients treated with intravenous Bor (ivBor), although the incidence and severity of PN in patients treated with sBor was lower than those in patients treated with ivBor [2‐4]. The most common Injection Site Reaction was erythema, however, only four patients (3 %) developed an Injection Site Reaction of grade 3 or more, necessitating a reduction in Bor dose in two (1 %) patients [3]. The Injection Site Reactions in the other two patients treated with sBor were severe, although detailed information regarding the clinical courses following these Reactions was not provided [3]. According to a classification of skin symptoms, Bor is classified as an irritant, as it causes extravasation of cytotoxic agents [5]. Further studies that focus on Injection Site Reaction of sBor, particularly in Japanese patients, are required. The present study retrospectively analyzed Injection Site Reactions in 19 Japanese patients with newly diagnosed (n = 9) or relapsed (n = 10) MM, and who were treated with sBor at a concentration of 2.5 mg/ml (3.0 mg Bor reconstituted with 1.2 ml normal saline), as described previously [3], between April 2011 and June 2012. We injected bortezomib to eight different Sites in the right and left abdomen, upper and lower quadrant, or right and left thigh, proximal and distal Sites of each patient in turn, as described previously [3]. These patients were treated with weekly BD (Bor 1.3 mg/m 2 on day 1, 8, 15, 22, and

Yong Chong - One of the best experts on this subject based on the ideXlab platform.

  • higher incidence of Injection Site Reactions after subcutaneous bortezomib administration on the thigh compared with the abdomen
    European Journal of Haematology, 2013
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Koichi Akashi
    Abstract:

    Subcutaneous (sc) rather than intravenous administration of bortezomib (Bor) is becoming more common for treating multiple myeloma (MM) because scBor results in lower incidence and severity of peripheral neuropathy and has equivalent efficacy. Bor is an irritant cytotoxic agent when it leaks out; therefore, it is recommended that Injections of scBor should be rotated among eight different Sites on the abdomen and thigh. However, detailed information about Injection Site Reaction (ISR) has not been sufficiently documented. We retrospectively analyzed the incidence and severity of ISR following scBor administration in 15 Japanese patients with MM. Grade 1 ISR occurred following 40 of 158 (25.3%) scBor Injections in ten patients, whereas grade 2 ISRs occurred following seven Injections (4.4%) in five patients. Five patients did not develop ISR. Of note, grade 2 ISR was documented in 6 of 65 (9.2%) thigh Injections but only in 1 of 93 (1.1%) abdominal Injections. These data show that grade 2 ISRs were more common in the thigh compared with the abdomen possibly because the thigh contains lesser adipose tissue than the abdomen. Grade 2 ISRs resolved without any sequela within a median of 7 d. scBor administration on the abdomen instead of the thigh should be considered, especially for emaciated patients, because ISR rapidly resolves within the interval before the next Injection even if it occurs.

  • Injection Site Reaction after subcutaneous administration of bortezomib in japanese patients with multiple myeloma
    International Journal of Hematology, 2012
    Co-Authors: Tomohiko Kamimura, Toshihiro Miyamoto, Shuichiro Takashima, Noriko Yokota, Yong Chong, Yoshikiyo Ito, Koichi Akashi
    Abstract:

    in patients treated with subcutaneous Bor (sBor) was nearly equal to that in patients treated with intravenous Bor (ivBor), although the incidence and severity of PN in patients treated with sBor was lower than those in patients treated with ivBor [2‐4]. The most common Injection Site Reaction was erythema, however, only four patients (3 %) developed an Injection Site Reaction of grade 3 or more, necessitating a reduction in Bor dose in two (1 %) patients [3]. The Injection Site Reactions in the other two patients treated with sBor were severe, although detailed information regarding the clinical courses following these Reactions was not provided [3]. According to a classification of skin symptoms, Bor is classified as an irritant, as it causes extravasation of cytotoxic agents [5]. Further studies that focus on Injection Site Reaction of sBor, particularly in Japanese patients, are required. The present study retrospectively analyzed Injection Site Reactions in 19 Japanese patients with newly diagnosed (n = 9) or relapsed (n = 10) MM, and who were treated with sBor at a concentration of 2.5 mg/ml (3.0 mg Bor reconstituted with 1.2 ml normal saline), as described previously [3], between April 2011 and June 2012. We injected bortezomib to eight different Sites in the right and left abdomen, upper and lower quadrant, or right and left thigh, proximal and distal Sites of each patient in turn, as described previously [3]. These patients were treated with weekly BD (Bor 1.3 mg/m 2 on day 1, 8, 15, 22, and