The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: Findings from clinical practice

Salar, Antonio; Haı̈oun, Corinne; Rossi, Francesca Gaia; Duehrsen, Ulrich; Pettengell, Ruth; Johnsen, Hans Erik; Jaeger, Ulrich; Verhoef, Gregor; Schwenkglenks, Matthias; Bacon, Pamela; Bendall, Kate; Lugtenburg, Pieternella J.

doi:10.1016/j.leukres.2012.02.002

Cited by 36 publications

(37 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This is slightly higher than the rate of 19% found in a large study of patients treated with standard R-CHOP. 25 Hyperglycemia and hyperlipidemia - toxicities observed in studies of continuous everolimus - were not a major issue (1 patient with grade 3 hyperglycemia; 3 with grade 3 hypertriglyceridemia) despite everolimus being administered with 5 days of prednisone. Everolimus can induce a drug rash and non-specific pneumonitis.…”

Section: Discussionmentioning

confidence: 99%

Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial

Johnston

LaPlant

McPhail

et al. 2016

The Lancet Haematology

View full text Add to dashboard Cite

Background The PI3K/mTORC pathway is upregulated in diffuse large B-cell lymphoma (DLBCL) and can be targeted with the mTORC1 inhibitor everolimus. Everolimus has activity in relapsed DLBCL. These data provide the rationale to combine everolimus with standard R-CHOP-21. Methods The primary endpoint of this study was to determine the maximum tolerated dose of everolimus 10 mg days 1-10 or 1-14 in combination with R-CHOP-21 for 6 cycles along with a feasibility cohort for response assessment in patients with new, untreated DLBCL. Secondary endpoints were the rate of event-free survival 12 months from registration and overall survival. Patients were considered evaluable for the primary endpoint in the phase I portion if they completed the first cycle as planned. In the feasibility portion all patients who received at least one dose of everolimus were included. This completed trial is registered with ClinicalTrials.gov as NCT01334502. Findings Nine patients were enrolled into the phase I trial without dose-limiting toxicities; therefore, everolimus 10 mg days 1-14 with standard R-CHOP-21 was tested in 15 additional patients for a total of 24 patients. The median age was 58.5 years (IQR, 49.5-71.5); 18 (75%) stages III/IV; 13 (54%) with elevated lactate dehydrogenase; 29% with high International Prognostic Index; and 54% (13/24) non-GCB by immunohistochemistry. The overall response rate was 96% (23/24; 95% CI: 79 – 100%) with 23 attaining functional complete remission by PET/CT (96%, 95% CI: 79 – 100%). The remaining patient went off study for refusal in cycle 1 and attained a complete response with RCHOP. The median follow-up is now 21.5 months (IQR, 17 - 29) with all 24 patients meeting EFS12. None of the 24 patients have died, and none have experienced relapse with DLBCL. The most common grade 3/4 toxicity was hematologic with 18 patients (75%) with grade 4 neutropenia of which five (21%) experienced grade 3 febrile neutropenia. Interpretation Everolimus for 14 days in combination with R-CHOP-21 is safe and produced a 96% CR rate in both GCB and non-GCB DLBCL. With a median follow-up of 21.5 months and all patients meeting EFS12, the lack of DLBCL relapse is of special interest. A randomized trial will be necessary to confirm the benefits of this novel combination. Funding National Cancer Institute of the United States; Novartis provided everolimus.

show abstract

Section: Discussionmentioning

confidence: 99%

Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial

Johnston

LaPlant

McPhail

et al. 2016

The Lancet Haematology

View full text Add to dashboard Cite

show abstract

“…Age was not identified as an independent risk factor for re-hospitalization and the incidence of FN in the present study. However, Lymam et al (5) and Salar et al (16) reported that an older age was an independent risk factor for the occurrence of FN. Therefore, elderly patients may require special attention concerning infection prevention.…”

Section: Resultsmentioning

confidence: 99%

Chemotherapy continuity and incidence of febrile neutropenia with CHOP therapy in an outpatient setting

Usami

Kimura

Iwai

et al. 2016

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. The cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) regimen is considered to be a standard treatment for non-Hodgkin's lymphoma (NHL). Patients receiving CHOP chemotherapy often experience febrile neutropenia (FN) due to myelotoxicity. The proper management of FN is essential to guarantee a positive outcome of the NHL treatment. Therefore, the present study retrospectively examined chemotherapy continuity and the incidence of FN during CHOP therapy in an outpatient setting. The subjects were 136 patients who received CHOP chemotherapy between January 2012 and December 2014. A total of 31 patients unable to be treated in an outpatient setting were excluded from the study. Of the remaining 105 patients, 73 patients who did not require hospitalization during the chemotherapy treatment were included in the non-hospitalized group, and 32 patients who required hospitalization during chemotherapy treatment were included in the re-hospitalization group. The numbers of patients from these two groups who completed the planned treatment were 71 and 24, respectively (P<0.01). In addition, the duration of granulocyte-colony stimulating factor (G-CSF) treatment was 5.3±1.22 and 6.1±1.46 days, respectively (P<0.01). The numbers of patients experiencing FN in an outpatient setting were 14 and 19, respectively (P<0.01). During administration of primary prophylaxis with G-CSF, the incidence of FN was 21.0% (22/105) in cycle 1. In conclusion, the present study has revealed a requirement to educate patients about infection prevention prior to the first cycle of chemotherapy. Patients who require the administration of long-term G-CSF are at risk of unplanned re-hospitalization, and treating them with polyethylene glycol G-CSF to reduce the number of required injections should be considered as an option. Therefore, proper supportive therapy and management of infection are important to safely treat patients with CHOP in an outpatient setting.

show abstract

“…The median duration of daily G-CSF use was only one day, indicating it was generally administered as short courses or intermittent doses during a cycle. This contrasts with the cytotoxic chemotherapy setting, where daily G-CSF is given typically consecutively on the first 5-6 days of the cycle [14,17]. Pegfilgrastim was used in around one-third of patients who received G-CSF, and pegfilgrastimtreated patients appeared to be more heavily pretreated and have more comorbidities than patients treated with daily G-CSF patients, while they were also younger and more received the standard dose of lenalidomide.…”

Section: Discussionmentioning

confidence: 99%

An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR‐MM)

et al. 2016

View full text Add to dashboard Cite

Neutropenia is a well‐known dose‐limiting toxicity associated with lenalidomide plus dexamethasone treatment in patients with multiple myeloma; however, little is known about its management and associated outcomes in the real world setting. The present prospective, multicenter, observational study evaluated the incidence, management, and outcomes of grade 3/4 neutropenia in patients with relapsed or relapsed/refractory multiple myeloma who initiated treatment with lenalidomide plus dexamethasone. Of 198 patients, 62 (31%, 95% CI: 25, 38) experienced grade 3/4 neutropenia, and half of these patients experienced 3 or more events during the 12‐month observational period. Grade 3/4 neutropenia occurred throughout lenalidomide treatment, with a median time to first event of 8.8 weeks (Q1, Q3: 5.9, 17.3). In a multivariate analysis, diagnosis of relapsed and refractory disease was associated with grade 3/4 neutropenia. Lenalidomide exposure reduction, use of G‐CSF, unplanned hospitalization, and outpatient clinic visits were more common in patients who experienced grade 3/4 neutropenia than in those who did not. In conclusion, grade 3/4 neutropenia is a common toxicity and patients are at continued risk throughout treatment with lenalidomide and dexamethasone. Further efforts should be made to improve the recommendations for neutropenia management in this population. Am. J. Hematol. 91:806–811, 2016. © 2016 Wiley Periodicals, Inc.

show abstract

The need for improved neutropenia risk assessment in DLBCL patients receiving R-CHOP-21: Findings from clinical practice

Cited by 36 publications

References 26 publications

Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial

Everolimus combined with R-CHOP-21 for new, untreated, diffuse large B-cell lymphoma (NCCTG 1085 [Alliance]): safety and efficacy results of a phase 1 and feasibility trial

Chemotherapy continuity and incidence of febrile neutropenia with CHOP therapy in an outpatient setting

An international, multicenter, prospective, observational study of neutropenia in patients being treated with lenalidomide + dexamethasone for relapsed or relapsed/refractory multiple myeloma (RR‐MM)

Contact Info

Product

Resources

About