Oncology nurses can help reduce the number of central line-associated bloodstream infections (CLABSIs) in patients undergoing hematopoietic stem cell transplant (HSCT) by standardizing central venous catheter (CVC) blood draws and chlorhexidine gluconate (CHG) treatment usage, according to a presentation at the 2022 Transplantation & Cellular Therapy Meetings.

Following a peer-to-peer observation and validation process was implemented in June 2021, there was a 68% decrease in CLABSI incidences at NYU Presbyterian 10 West. The number of incidences improved from 2.82 events per 1000 central line days (pre-intervention January to May) to 0.90 events per 1000 central line days (June to August).

“Oncology nurses play a primary role in implementing strategies to help reducing preventable CLABSI,” Thanyanee McNinney, BSN, RN, OCN, of the New-York Presbyterian Department of Nursing, said in a poster presentation of the findings.

CLABSIs represent a significant mortality risk to patients and are also linked with financial toxicities; one case of CLABSI can cost around $40,000.

Furthermore,factors including long term central line placement and usage, high-dose chemotherapy, prolonged immunosuppression, and the possibility of posttransplant complications such as graft-vs-host-disease (GVHD) mean that patients undergoing HSCT are especially vulnerable to CLASBI. However, research has demonstrated that proper insertion techniques and central line management can help prevent CLABSI.

In 2020, there were 0.51 CLABSIs per 1000 central line days at the investigator’s institution; by the second quarter of 2021, there were 2.82 CLABSIs per 1000 central line days.

Therefore, investigators sought to increase competency and reduce the incidence at their institution. Their objective was to reduce incidence by 20% within 3 months on a 16-bed HSCT inpatient unit in an academic medical center.

Investigators collaborated with the Hospital Acquired Infection (HAI) champions and nursing leadership teams to develop an action plan. This plan consisted of a thorough root to cause analysis of incidences, interdisciplinary huddles, standardized validation tools to allow peer-to-peer observation and validation during blood culture and blood specimen collection via central lines and CHG use.

The CVL peer feedback tool assessed whether observed staff performed proper hand hygiene when indicated, needle endcaps were clean, CVC ports/lines not being used had an alcohol impregnated endcap in place, all intravenous (IV) tubing not being used had a red cap, that no IV tubing were expired and had adequate labels indicating last line change, and that the CVC dressings were clean, intact, and not reinforced.

Following peer-to-peer observation and validation, it was revealed that 35% of nurses did not adhere to NYP policy when collecting blood cultures or drawing blood via a central line. Furthermore, 66% of nurses did not know how to perform CHG treatments correctly.

In addition, the study revealed multiple opportunities for growth. Among some of the registered nurses, peers observed the donning of gloves without performing hand hygiene, opening equipment without proper aseptic technique; insufficient scrubbing of the hub, failure to replace new Q-site prior to drawing blood cultures, drawing blood cultures directly through the lumen without a new Q-site placement, and a failure to flush with required amount of normal saline post-blood draw and performing push-pause technique when flushing.

Ultimately, nurses can be pivotal in reducing CLABSIs by educating staff members on proper CHG wipe usage and standardizing central line blood draws. These efforts are consistent with the “zero harm” initiative adopted at various institutions and represents a commitment to providing a safe and caring environment for patients and staff by eliminating all preventable patient injuries and infections.

McNinney T, Roselli T, Miner D. Reducing central line-associated bloodstream infections (CLABSI) through standardizing central venous catheter (CVC) blood draws and chlorhexidine gluconate (CHG) treatment usage. Presented at: 2022 Tandem Meetings Transplantation & Cellular Therapy Meetings of ACTCT and CIBMTR; April 23-26, 2022; Salt Lake City, UT. Abstract 612. 

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Oncology nurses at the 2022 ASTCT Meeting shared how a peer-to-peer observation and validation tool helped decrease central line-associated bloodstream infections by 68%.



Oncology Nurses Drastically Reduce Central Line Infection Incidences Through Peer-to-Peer Observation Strategy

At a 2-year follow-up, lisocabtagene maraleucel (liso-cel; Breyanzi) continued to yield positive outcomes in patients with relapsed/refractory large B-cell lymphomas (LBCL), according to results from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) presented during the 2022 Transplantation & Cellular Therapy Meetings.

Treatment with liso-cel elicited an overall response rate (ORR) of 73% (95% CI, 66.9%-78.1%), including a complete response (CR) rate of 53% (95% CI, 46.6%-59.2%) among 257 efficacy-evaluable patients after a median follow-up of 23.0 months. The median duration of response (DOR) by Lugano 2014 criteria was 23.1 months (95% CI, 8.6–not reached [NR]) and the probability of continued response at 2 years was 49.5% (95% CI, 41.4%-57.0%).

Additionally, the median DOR was 26.1 months (95% CI, 23.1–NR) and 23.1 months (95% CI, 5.6-NR) in those who achieved a CR and partial response (PR), respectively.

“This 2-year follow-up analysis of TRANSCEND demonstrated durable response to liso-cel in patients with high-risk aggressive relapsed/refractory LBCLs,” Jeremy Abramson, MD, director of the Jon and Jo Ann Hagler Center for Lymphoma, Massachusetts General Hospital, and an associate professor of medicine at Harvard Medical School said during the presentation. “Liso-cel treatment was associated with a low incidence of severe cytokine release syndrome [CRS] and neurologic events,” Abramson added.

To be eligible for the study, patients needed to be 18 years or older and have received 2 or more prior lines of therapy. Those who enrolled had diffuse large B-cell lymphoma that was not otherwise specified (DLBCL NOS)—either de novo or transformed from follicular lymphoma, marginal zone lymphoma, or another disease—high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMLBCL), or follicular lymphoma grade 3B (FL3B). Other inclusion criteria included previous hematopoietic stem cell transplant and an ECOG performance status of 0 or 2. Primary central nervous system lymphoma was also allowed.

Patients received a lymphodepleting regimen of 30 mg/m2 fludarabine and 300 mg/m2 of cyclophosphamide for 3 days followed by liso-cel 2 to 7 days later. The on-study follow up was 24 months.

The study’s primary end points were adverse effects (AE) and ORR by independent review committee (IRC). Secondary end points included CR rate by IRC, DOR, progression-free survival (PFS), overall survival (OS), and pharmacokinetic profile.

Patients who enrolled on the trial were followed for 2 years after the last liso-cel dose, and the study is ongoing as of the cutoff date of January 2021. Two hundred and sixty-eight patients had died or withdrawn 24 months or more after follow-up. Among 120 patients who completed the study, 81 agreed to be part of a long-term follow-up study assessing safety and OS up to 15 years, but no IRC response assessments were performed.

Notably, 1 patient died following an ongoing CR at 26 weeks due to sepsis. No patients relapsed after 23 months in the study.

The median patient age was 63 years and 41% of patients were aged 65 years or older. The majority of patients had DLBCL NOS (51%), and others had transformed follicular lymphoma (22%), other indolent lymphomas (7%), HGBCL (13%), PMBCL (6%), and FL3B (1%). Additionally, most patients were chemotherapy refractory (67%) and underwent treatment with a bridging therapy (59%). The overall median follow up was 19.9 months.

Additional findings from the study indicated that after a median follow-up of 23.9 months, the median PFS was 6.8 months (95% CI, 3.3-12.7) and the probability of PFS at 2 years was 40.6% (95% CI, 34.0%-47.2%). The median PFS in those who had a CR and PR was 27.3 months (95% CI, 24.0-NR) and 6.8 months (95% CI, 3.3-12.7).

After a median follow-up of 29.3 months, the median OS was 27.3 months (95% CI, 16.2-45.6), with a 2-year probability of OS rate of 50.5% (95% CI, 44.1%-56.5%). The median OS in those who had a CR or PR was 48.5 months (95% CI, 45.2-NR) and 9.0 months (95% CI, 6.0-11.4), respectively. In non-responders, the median OS was 5.4 months (95% CI, 2.9-6.5). Three deaths occurred after 45 months. Moreover, CAR T-cell persistence was detected at 48 months in the long-term follow-up study (NCT03435796) in addition to 37% of patients at 24 months in the TRANSCEND study.

In terms of safety, the most common any AEs within 90 days of infusion were neutropenia (63%), anemia (48%), and fatigue (44%), and grade 3 or higher AEs include neutropenia (60%), anemia (37%), and thrombocytopenia (27%). Any grade and grade 3 or higher infections occurred in 12% of patients, and in 41% of patients with any grade AE. From day 91 to the end of study, the most common any grade AEs were neutropenia (8%), anemia (8%), and fatigue (7%), with grade 3 or higher AEs including neutropenia (7%), anemia (6%), and thrombocytopenia (4%). Any grade and grade 3 or higher infections occurred in 5% of patients, and in 10% of patients with any grade AE.

Investigators reported several AEs of special interest. Any grade and grade 3/4 CRS were reported in 42% and 2% of patients, respectively; the median time to onset and resolution of CRS was 5 days, respectively. Any grade and grade 3/4 neurologic events were reported in 30% and 10% of patients, respectively. The median time to onset was 9 days and the median time to resolution was 11 days. Most cases of CRS and neurological events were grade 1/2, with no grade 5 events.

Second primary malignancies (SPM) occurred in 5 and 17 patients during the treatment emergent and post–treatment emergent periods, respectively. The types and incidence of SPMs were expected given the patient population and prior therapies and included diseases such as non-melanoma skin cancer (n = 9), solid tumors (n = 4), myelodysplastic syndrome (n = 8), acute myeloid leukemia (n = 2), and peripheral T-cell lymphoma (PTCL; n = 1). The single case of PTCL was reported on day 30 and did not appear to be in relation to treatment with liso-cel.

Of 270 patients, 9 died 30 days or less following last infusion, 24 died at over 30 days to 90 days or less, and 100 died at over 90 days. The majority of deaths were attributed to disease progression and no deaths were due to COVID-19.

Abramson JS, Palomba ML, Gordon LI, et al. Two-year follow-up of TRANSCEND NHL 001, a multicenter phase 1 study of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphomas. Presented at: 2022 Transplantation & Cellular Therapy Meetings; April 23-26, 2022. Abstract 65.

Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. 

. 2014;32(27):3059-3068. doi:10.1200/JCO.2013.54.8800

Patients with relapsed/refractory large B-cell lymphoma continued to derive benefit from lisocabtagene maraleucel after 2 years of follow-up.

Liso-cel Exhibits Durable Responses in Relapsed-Refractory Large B-Cell Lymphoma

Patients with relapsed or refectory large B-cell lymphoma (LBCL) who received axicabtagene ciloleucel (axi-cel; Yescarta) continued to elicit a long-term survival overall survival (OS) benefit at 5-year follow-up, according to data from an analysis of the phase 2 ZUMA-1 trial (NCT02348216) presented during the 2022 Tandem Meeting.

“In this updated 5-year analysis, axi-cel induced long-term OS...among treated patients,” according to Caron A. Jacobson, MD, MMSc, medical director of the Immune Effector Cell Therapy Program and senior physician at Dana-Farber Cancer Institute. “Between the 4- and 5-year analysis, the time to next therapy curve remains stable and 92% of patients remained alive without a need for subsequent therapy, which may be suggestive of a cure in these patients,” said Jacobson, who is also an assistant professor of medicine at Harvard Medical School.

Investigators reported a 5-year OS rate of 42.6% (95% CI, 32.8%-51.9%) following treatment with axi-cel (n = 101). In the population of patients who experienced a complete response, the 5-year OS rate was 64.4% (95% CI, 50.8%-75.1%) and the median OS was not reached (95% CI, 63.4–not estimated). Additionally, 63% of complete responders were alive at the 5-year data cut off. At the 4-year data cutoff, 1 patient died at month 63 and one experienced progressive disease at month 54.

To be considered for treatment, patients were required to have LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma. Patients were also required to have not responded to their last chemotherapeutic or have relapsed 12 months or less following autologous stem cell transplant. Treatment with a previous anti-CD20 monoclonal antibody and anthracycline was also necessary.

Those who underwent treatment received a conditioning regimen of cyclophosphamide at 500 mg/m

 of fludarabine for 3 days. This was followed by axi-cel at a dose of 2x106 CAR T-cells/kg. The primary end point was overall response rate with first response assessment 4 weeks following infusion, Key secondary end points included OS, safety, and translational evaluations.

A total of 111 patients were enrolled on the study, 8 of whom did not undergo treatment due to adverse effects (AEs; n = 4), no measurable disease (n = 2), death due to disease progression (n = 1), and manufacturing failure (n =1); this left 103 patients to undergo conditioning. Of these patients 2 were not treated due to AEs and death, respectively. One hundred and three patients underwent infusion. The data cutoff was August 11, 2021 and the median follow-up was 63.1 months.

Additional findings from the trial highlighted a median time to next anticancer therapy of 8.7 months following infusion. A total of 34% of patients were alive at cutoff with no subsequent therapy or retreatment with axi-cel. Two patients who had prior progression underwent new anticancer therapy.

According to results of an exploratory analysis, investigators reported that 1- and 2-year event-free survival (EFS) may potentially have a role as a surrogate end point for long-term OS. The 5-year OS rates among those who had or had not experienced an EFS event at month 12 were 5.3% vs 90.9%, respectively. The median OS was 8.3 months among those who experienced an event and was not reached in those who did not experience an event. Additionally, the 5-year OS rates among those who did or did not have an EFS event at month 24 were 11.3% and 92.3%, respectively. Moreover, the median OS in both respective groups was 9.2 months and not reached.

Investigators also determined that early CAR T-cell expansion was associated with ongoing response at 60 months. The median peak CAR T levels appeared to be numerically higher in those who had an ongoing response at month 60 and lower in those who relapsed or did not respond to treatment. Similarly, another trend was observed in those who experienced CAR T-cell expansion by area under the curve from day 0 to 28.

A total of 58% of patients had died by the cutoff date. No new safety signals had been observed as of the 5-year data cutoff, including serious AEs or secondary malignancies related to treatment. Patients most commonly died due to progressive disease (n = 45), AEs (n = 4), secondary malignancies (n = 1), or other reasons (n = 9).

Jacobson C, Locke FL, Ghobadi A, et al. Long-term (5 year) overall survival in Zuma-1, the pivotal study of axicabtagene ciloleucel (Axi-Cel) in patients with refractory large B-cell lymphoma (LBCL). Presented at: 2022 Tandem Meetins; April 23-26, 2022; Salt Lake City, UT. Abstract 10.

Patients with relapsed or refractory large B-cell lymphoma experienced improved overall survival following treatment with axicabtagene ciloleucel.

 Axi-cel Sustains Long-Term Survival Rates in Relapsed/Refractory Large B-Cell Lymphoma 

Belimumab (Benlysta) may be a useful treatment for the prevention of chronic graft-vs-host-disease (cGVHD) in patients undergoing allogeneic hematopoietic transplantation, although a larger confirmatory trial is still warranted, according to study results presented at the 2022 ASTCT Meeting.

Belimumab, which is FDA approved for adults with systematic lupus erythematosus and active lupus nephritis, was found to be very well tolerated and also was not linked to any severe infections or myelosuppression when administered to patients in remission from hematologic malignancies.

Overall, 2 out of the 9 patients who received belimumab on study developed moderate to severe cGVHD. One patient died and the other did have an initial response to therapy.

“These data describe, for the first time, [the] use of belimumab for chronic GVHD prophylaxis,” Iskra Pusic, MD, MSCI, of the Division of Oncology at Washington University School of Medicine in St. Louis, noted in a presentation of the findings. “Belimumab was very well tolerated, and the absence of severe infections and myelosuppression is very reassuring.”

Belimumab is a human monoclonal antibody that functions by preventing B-cell activating factor (BAFF) from binding to its receptors on B cells, thus preventing aforeactive B cells from surviving. Because B cells play an important role in cGVHD pathophysiology and because BAFF plays a substantiated role in cGVHD by promoting BCR signaling, investigators hypothesized that belimumab could be effective at prevention of this disease.

“The coordinated interaction and response between T cells and B cells are required for further perpetuation of chronic GVHD,” Pusic explained. “We know that selective modulation of this alloreactive response rather than general immunosuppression would be a promising mechanism for prevention of GVHD, while still allowing and preserving [the] graft-vs-leukemia effect.”

To that end, this single-center, investigator-initiated phase 1 trial enrolled 9 patients with acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), myelodysplastic syndromes (MDS), and lymphoma to evaluate whether targeting BAFF early after allogenic hematopoietic transplant would have a favorable effect on the incidence or severity of cGVHD.

Enrolled patients were adults in complete remission and tested negative for minimal residual disease 30 days after transplant. Patients had received mobilized peripheral blood stem cells from 10/10 haploidentical-matched related or unrelated donors. Cells received either myeloablative or non-myeloablative conditioning, and tacrolimus, methotrexate, and antithymocyte globulin were allowed. Seven out of the 8 patients were treated with ATG and 1 was treated with posttransplant cyclophosphamide.

Patients received belimumab at 10 mg/kg every 2 weeks for 3 doses followed by 4 more doses at monthly intervals. Treatment initiation began 50 to 80 days following allogeneic hematopoietic cell transplantation.

Patients who received at least 1 dose were evaluable for safety, and patients who received at least 2 doses were evaluable for both safety and efficacy.

The median follow-up time after transplant was 28 months (range, 12-43); the median time since belimumab completion was 23 months (range, 4-29).

Eight of 9 patients successfully received all 7 of the preplanned doses of belimumab. After more than 20 months of follow-up (range, 20-29 months), 5 are alive with no evidence of cGVHD.

Two patients developed cGVHD of the skin, eye, mouth, and liver. For 1 patient, this occurred following their fifth cycle of belimumab; however, their condition improved through treatment with tacrolimus, ruxolitinib (Jakafi), and steroids administered via a tapered schedule. Unfortunately, the other patient died from pneumonia complications after cGVHD occurred 2 months beyond their last belimumab cycle.

Another patient completed all 7 cycles but relapsed with AML 1 month later and was treated with enasidenib (Idhifa) and donor lymphocyte infusion. This patient is now 16 months posttreatment and receiving prednisone for mild oral and upper gastrointestinal cGVHD.

One patient experienced thrombocytopenia and consequently had to reduce their dose to 3 cycles—3 months later, this patient relapsed with lymphoma. Three patients developed stage 1 skin acute GVHD; 2 cases resolved completely with a steroid pulse, and 1 case developed into overlap cGVHD.

No adverse events equal to or greater than grade 3 were reported. There were also no signification infections or myelosuppression, although 1 patient had cytomegalovirus reaction. No patients demonstrated any infusion reactions or hypersensitivity.

“While the result of our study really needs further validation in a larger trial to further assess the impact of belimumab on incidences of chronic GVHD, these preliminary results are encouraging,” Pusic said.

Furthermore, risk stratification should be an important consideration in future studies, she concluded, noting that correlative studies have been launched because B-cell reconstitution was delayed.

Pusic I, Johanns T, Sarantopoulos S, et al. Use of belimumab for prophylaxis of chronic graft-versus-host disease. Presented at: 2022 Tandem Meetings Transplantation & Cellular Therapy Meetings of ACTCT and CIBMTR; April 23-26, 2022; Salt Lake City, UT. Abstract 34.

Belimumab has emerged as a safe and tolerable agent that may be useful for the prophylaxis of chronic graft-vs-host-disease.

Transplantation and Cellular Therapy Meetings

Oncology Nurses Drastically Reduce Central Line Infection Incidences Through Peer-to-Peer Observation Strategy

Liso-cel Exhibits Durable Responses in Relapsed-Refractory Large B-Cell Lymphoma

Axi-cel Sustains Long-Term Survival Rates in Relapsed/Refractory Large B-Cell Lymphoma

Belimumab May Help Prevent Chronic GVHD in Adults Undergoing Allogenic Transplant