scholarly journals Real-World Use of Isavuconazole as Primary Therapy for Invasive Fungal Infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant

2022 ◽  
Vol 8 (1) ◽  
pp. 74
Author(s):  
Hiba Dagher ◽  
Ray Hachem ◽  
Anne-Marie Chaftari ◽  
Ying Jiang ◽  
Shahnoor Ali ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Combination Therapy ◽  
Real World ◽  
Fungal Infections ◽  
Hematologic Malignancies ◽  
Invasive Fungal Infections ◽  
Cell Transplant ◽  
Primary Therapy ◽  
Significant Difference

(1) Introduction: Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety. (2) Methods: We conducted a retrospective study of HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between 1 April 2016 and 31 January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up. (3) Results: We included 200 HM patients with IFIs that were classified as definite (11), probable (63) and possible (126). Aspergillus spp was the most commonly isolated pathogen. The majority of patients (59%) received prophylaxis with anti-mold therapy and Isavuconazole was used as a primary therapy in 43% of patients, and as salvage therapy in 58%. The switch to Isavuconazole was driven by the failure of the primary therapy in 66% of the cases and by adverse effects in 29%. Isavuconazole was used as monotherapy in 30% of the cases and in combination in 70%. Adverse events possibly related to Isavuconazole were reported in eight patients (4%) leading to drug discontinuation. Moreover, a favorable response with Isavuconazole was observed in 40% at 6 weeks and in 60% at 12 weeks. There was no significant difference between isavuconazole monotherapy and combination therapy (p = 0.16 at 6 weeks and p = 0.06 at 12 weeks). Finally, there was no significant difference in outcome when Isavuconazole was used after failure of other anti-mold prophylaxis or treatment versus when used de novo as an anti-mold therapy (p = 0.68 at 6 weeks and p = 0.25 at 12 weeks). (4) Conclusions: Whether used as first-line therapy or after the failure of other azole and non-azole prophylaxis or therapies, isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high-risk cancer patients with hematologic malignancies. Moreover, combination therapy did not improve the outcome compared to Isavuconazole therapy.

scholarly journals 1182. The Real-World Use of Isavuconazole as Primary or salvage Therapy of Invasive Fungal infections in High-Risk Patients with Hematologic Malignancy or Stem Cell Transplant

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S616-S616
Author(s):  
Hiba dagher ◽  
Ray Y Hachem ◽  
Anne-Marie Chaftari ◽  
Ying Jiang ◽  
Shahnoor Ali ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Adverse Events ◽  
Real World ◽  
Salvage Therapy ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Primary Therapy ◽  
Material Support ◽  
Prolonged Qt

Abstract Background Invasive fungal infections (IFIs) are a major cause of morbidity and mortality among immunocompromised patients with hematologic malignancies (HM) and stem cell transplants (SCT). Isavuconazole was approved by FDA as a primary therapy for Invasive Aspergillosis (IA) and Mucormycosis. The aim of this study is to look at the real-world use of Isavuconazole in patients with HM and evaluate their clinical outcomes and safety. Methods We conducted a retrospective study of 200 HM patients at MD Anderson Cancer Center who had definite, probable or possible mold infections between April 2016 and January 2020 and were treated with Isavuconazole for a period of at least 7 days. Clinical and radiological findings were assessed at baseline and at 6 and 12 weeks of follow up. Results HM patients with IFIs were classified as definite (11), probable (66) and possible (123). IA was the most commonly isolated pathogen followed by mucor and candida. The majority of patients (65%) received prophylaxis with anti-mold therapy, 73% consisted of azoles and 22% of echinocandins. Isavuconazole was used as a primary therapy in 57.5% of patients, and as salvage therapy in 42.5%. The switch to Isavuconazole was driven by failure of the primary therapy in 50% of the cases and by adverse effects in 28%. These included elevated liver function tests (LFTs), subtherapeutic voriconazole levels and prolonged QT. Isavuconazole was used as monotherapy in 30% of the cases and combination in 70% mostly with a polyene (54%) and/or an echinocandin (27%). A favorable response with Isavuconazole was observed in 57% at 6 weeks of therapy. Adverse events possibly related to Isavuconazole were reported in 6 patients (3%) leading to drug discontinuation. These included 5 elevated transaminases and 1 nausea. All-cause mortality was reported in 46% of patients and IFI-attributable mortality in 25%. Conclusion Selecting Isavuconazole therapy was mainly driven by failure of other antifungal agents or adverse events to other antifungals such as increased LFTs, subtherapeutic voriconazole levels or prolonged QT. Isavuconazole seems to have a promising clinical response and a good safety profile as an antifungal therapy in high risk cancer patients with HM. Disclosures Issam I. Raad, MD, Citius (Other Financial or Material Support, Ownership interest)Cook Medical (Grant/Research Support)Inventive Protocol (Other Financial or Material Support, Ownership interest)Novel Anti-Infective Technologies (Shareholder, Other Financial or Material Support, Ownership interest)

scholarly journals Randomized Comparison of Safety and Pharmacokinetics of Caspofungin, Liposomal Amphotericin B, and the Combination of Both in Allogeneic Hematopoietic Stem Cell Recipients

2010 ◽  
Vol 54 (10) ◽  
pp. 4143-4149 ◽  
Author(s):  
Andreas H. Groll ◽  
Gerda Silling ◽  
Charlotte Young ◽  
Rainer Schwerdtfeger ◽  
Helmut Ostermann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Combination Therapy ◽  
Adverse Events ◽  
Amphotericin B ◽  
Hematopoietic Stem Cell ◽  
Liposomal Amphotericin ◽  
Fungal Infections ◽  
Study Drug ◽  
Invasive Fungal Infections ◽  
Hematopoietic Stem

ABSTRACT The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacokinetics of the combination of LAMB and CAS were investigated in a risk-stratified, randomized, multicenter phase II clinical trial in 55 adult allogeneic hematopoietic stem cell recipients (aHSCT) with granulocytopenia and refractory fever. The patients received either CAS (50 mg/day; day 1, 70 mg), LAMB (3 mg/kg of body weight/day), or the combination of both (CASLAMB) until defervescence and granulocyte recovery. Safety, development of invasive fungal infections, and survival were assessed through day 14 after the end of therapy. Pharmacokinetic sampling and analysis were performed on days 1 and 4. All three regimens were well tolerated. Premature study drug discontinuations due to grade III/IV adverse events occurred in 1/18, 2/20, and 0/17 patients randomized to CAS, LAMB, and CASLAMB, respectively. Adverse events not leading to study drug discontinuation were frequent but similar across cohorts, except for a higher frequency of hypokalemia with CASLAMB (P < 0.05). Drug exposures were similar for patients receiving combination therapy and those randomized to monotherapy. There was no apparent difference in the occurrence of proven/probable invasive fungal infections and survival through day 14 after the end of therapy. CASLAMB combination therapy in immunocompromised aHSCT patients was as safe as monotherapy with CAS or LAMB and had similar plasma pharmacokinetics, lending support to further investigations of the combination in the management of patients with invasive opportunistic mycoses.

scholarly journals RhizomucorandScedosporiumInfection Post Hematopoietic Stem-Cell Transplant

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Dânia Sofia Marques ◽  
Carlos Pinho Vaz ◽  
Rosa Branca ◽  
Fernando Campilho ◽  
Catarina Lamelas ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Increased Risk

Hematopoietic stem-cell transplant recipients are at increased risk of developing invasive fungal infections. This is a major cause of morbidity and mortality. We report a case of a 17-year-old male patient diagnosed with severe idiopathic acquired aplastic anemia who developed fungal pneumonitis due toRhizomucor sp.and rhinoencephalitis due toScedosporium apiospermum6 and 8 months after undergoing allogeneic hematopoietic stem-cell transplant from an HLA-matched unrelated donor. Discussion highlights risk factors for invasive fungal infections (i.e., mucormycosis and scedosporiosis), its clinical features, and the factors that must be taken into account to successfully treat them (early diagnosis, correction of predisposing factors, aggressive surgical debridement, and antifungal and adjunctive therapies).

Outcomes of invasive fungal infections in hematopoietic stem cell transplant patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18008-e18008
Author(s):  
Shagufta Shaheen ◽  
Shivanck Upadhyay ◽  
Creticus Petrov Marak ◽  
Gagan Kumar ◽  
Achuta Kumar Guddati
Keyword(s):  
Stem Cell ◽  
Fungal Infection ◽  
Hospital Stay ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Fungal Infections ◽  
Length Of Hospital Stay ◽  
Invasive Fungal Infections ◽  
Cell Transplant ◽  
Hematopoietic Stem

e18008 Background: Invasive fungal infections are associated with higher mortality in hematopoietic stem cell transplant (HSCT) recipients despite the use of broad spectrum antifungal agents. With the increase in the number of patients undergoing HSCT and a newer array of immunosuppressants, it is necessary to examine the incidence and outcomes of fungal infection in this population. Methods: We used Nationwide Inpatient Sample from years 2000 to 2008 to examine the trends and outcomes of fungal infections in patients admitted for HSCT. We used ICD-9-CM codes to identify those with HSCT. Similarly we identified invasive fungal infection using ICD-9-CM codes. The engraftment period and subsequent admissions were examined separately. Outcomes studied were in-hospital mortality and length of hospital stay. Logistic regression analysis was used to identify independent association of fungal infection with mortality. The model was adjusted for demographic and hospital characteristics, Charlson's co-morbidity index and severity of sepsis using number of organ failures. Results: There were 291,182 admissions with HSCT from 2000 to 2008. Of these, 3.4% patients had invasive fungal infections. They were more frequent in allogenic transplant during the engraftment period (4.2%) and in those with graft versus host disease (GVHD) in subsequent admission (7.1%). The unadjusted in-hospital mortality was significantly higher in those with invasive fungal infection (28% vs. 7%, p<0.001). On adjusted analysis, the odds of mortality were highest for those with mucor (OR 4.3;95%CI 2.5-7.5) and aspergillus (OR 3.7; 95%CI 3.1-4.5) infections while the results did not reach significance for candidemia. The length of hospital stay was significantly longer in those with invasive fungal infections (median 19 days vs. 7 days, p<0.001). Conclusions: Fungal infections are common in HSCT recipients - especially in those with allografts and with GVHD. Mortality is high and is mostly associated with aspergillus and mucor. A higher index of suspicion for fungal infections in HSCT patients, strict isolation precautions and increased surveillance for aspergillus and mucor in HSCT patients may help decrease the length of hospital stay and mortality.

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