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Abstract

Background:

Brentuximab vedotin (BV) and polatuzumab vedotin (PV), CD30-specific and CD79b-specific monoclonal antibody conjugates, respectively, are used in the treatment of hematologic cancers. Both have been observed to cause gastrointestinal adverse events (GI AEs).

Objectives:

We aimed to assess the clinical characteristics, disease course, treatment, and outcomes of patients who developed GI AEs following treatment with BV or PV.

Design:

We retrospectively identified 879 adult cancer patients who received BV or PV therapy between March 1, 2016, and March 31, 2023, at our tertiary cancer center. Patients with alternate diagnoses were excluded.

Methods:

Clinical characteristics, management, and outcomes of GI AEs were retrospectively evaluated and statistically analyzed.

Results:

Sixty-four patients were included, and the median duration from therapy initiation to GI AE onset was 37 days. GI AEs occurred in the lower gastrointestinal tract (78%), upper gastrointestinal tract (45%), hepatobiliary system (11%), and pancreatic system (4.3%). Common symptoms were diarrhea (77%), nausea (61%), and abdominal pain (52%). Some patients had Common Terminology Criteria for Adverse Events grade ⩾3 toxicity (19% with diarrhea and 2.7% with colitis symptoms). Most patients (81%) received supportive care alone, and three received corticosteroids. Most patients (93%) achieved symptom resolution following treatment. Symptoms recurred in 37% of patients, and 41% of patients stopped BV/PV therapy due to GI AE.

Conclusion:

GI AEs following the use of targeted antibody–drug conjugates can involve various gastrointestinal systems. In our patient cohort who received BV or PV, GI AEs were typically low grade and managed with supportive care or corticosteroids. Nonetheless, some patients experienced high-grade AEs or symptom recurrence and stopped BV/PV therapy. Future studies may provide clarification and guide clinical practice.

Keywords

brentuximab vedotin gastrointestinal adverse event monoclonal antibody–drug conjugate polatuzumab vedotin

Introduction

Gastrointestinal adverse events (GI AEs) can occur with many types of cancer therapies, including those with immune checkpoint inhibitors (ICIs), whose adverse effects have been well studied.^1,2 Brentuximab vedotin (BV) and polatuzumab vedotin (PV), CD30-specific and CD79b-specific monoclonal antibody–drug conjugates, respectively, have been approved for the treatment of select hematologic malignancies, such as systemic anaplastic large-cell lymphoma, Hodgkin lymphoma, and diffuse large B-cell lymphoma.^3–7 In clinical trials using these drugs, common GI AEs included diarrhea, nausea, and vomiting, and some patients experienced high-grade AEs.^4–7 Colitis related to BV therapy has been described in multiple recent case reports with endoscopic findings of both ulcerative and non-ulcerative inflammation.^8–10 In these reports, the predominant histopathologic findings included cryptitis and apoptotic colopathy.^8–10 The mechanism by which BV and PV may cause gastrointestinal inflammation remains unclear but may be related to these drugs’ immunologic effects. This speculation is supported by reports of brentuximab-induced colitis that is responsive to corticosteroid therapy.⁹

While BV and PV have been the focus of some clinical studies and case reports, the GI AEs of BV and PV have not yet been studied in a cohort study. Furthermore, the optimal management of GI AEs secondary to BV or PV therapy is unestablished. Thus, we assessed the clinical characteristics, disease course, treatment, and outcomes of patients who developed GI AEs following treatment with BV or PV at a single tertiary cancer center.

Methods

Patient selection and data collection

We obtained Institutional Review Board approval to perform a retrospective, single-center study including patients with cancer who underwent BV or PV therapy and subsequently had gastrointestinal toxicity between March 1, 2016, and March 31, 2023. Patients were included in the study if they (1) were at least 18 years old; (2) had a cancer diagnosis; (3) underwent therapy with BV or PV; and (4) had evidence of at least one GI AE based on symptom presentation or endoscopy findings after receiving BV or PV therapy. We excluded patients whose gastrointestinal events were determined to have alternative etiologies, such as infection or chronic gastrointestinal disease. The decision was based on the best judgment after a thorough review of medical documentation. We extracted demographic data (including age, sex, and race), oncological data (including cancer type, cancer stage, and prior and other concurrent cancer treatment), and medical comorbidities from the patients’ electronic health records. Cancer stage was determined according to the Ann Arbor Staging System for nodal lymphomas and Global Response Criteria for cutaneous T-cell lymphomas as described in the American Joint Committee on Cancer’s Cancer Staging Manual, 8th edition.¹¹ The reporting of this study conforms to the STROBE statement¹² (Supplemental File 1).

Evaluation and diagnosis of GI AEs

The duration and severity of the GI AEs, including diarrhea and colitis, were assessed based on the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0.¹³ The presence of other gastrointestinal symptoms, such as nausea, vomiting, or abdominal pain, was recorded. The positive result of fecal inflammatory markers, such as lactoferrin and calprotectin, was recorded. Initial and follow-up endoscopic findings and histopathological findings were documented when available, based on information presented in the procedure and histopathology reports found in the medical record. The endoscopic findings were classified as ulcerative inflammation, non-ulcerative inflammation (e.g., erythema, friability, erosions, inflammatory exudate, loss of vascular pattern, and edema), or normal. Histopathological findings were categorized as normal, acute active colitis (e.g., cryptitis, crypt abscess, apoptosis, eosinophilic infiltration, and intraepithelial neutrophil infiltration), chronic active colitis (e.g., crypt architectural distortion, basal lymphoplasmacytosis, and paneth cell metaplasia), or microscopic colitis (e.g., intraepithelial lymphocytic infiltration and subepithelial collagen bands). These findings were classified by A.G.K., M.S., J.S.S., N.M., and S.N. using previously published methods.¹⁴

Treatment of GI AEs and outcomes

Data on the treatment of diarrhea and colitis included the use of supportive measures, such as anti-diarrheal and non-immunosuppressive anti-inflammatory agents (e.g., loperamide, cholestyramine, and mesalamine) and immunosuppressive agents (e.g., corticosteroids). The clinical outcomes of GI AEs included the duration of treatment for the GI AE, the need for hospitalization, the duration of hospitalization, symptom response (defined as resolution of symptoms or improvement of the symptoms to CTCAE grade 1), and remission (defined as the maintenance of symptom response following completion of corticosteroid taper), the recurrence of gastrointestinal symptoms, cancer therapy resumption, and all-cause mortality.

Statistical analysis

Categorical variables were represented by percentages, and continuous variables were represented using medians and interquartile ranges. Categorical variables were compared using Fisher’s exact tests. Continuous variables were compared using Mann–Whitney U tests. p Values of 0.05 or less were considered statistically significant. Statistical analyses were conducted using SPSS version 26.0.

Results

Patient characteristics

Of the 879 adult cancer patients who received either BV or PV therapy at our tertiary cancer center between March 1, 2016, and March 31, 2023, 815 patients did not meet the inclusion criteria; 64 patients were ultimately included in the study (Figure 1). The characteristics of these patients are shown in Table 1. Their median age was 55 years, and 50% of patients were male. Most patients were white (69%), and the median Charlson Comorbidity Index was 6. The most common malignancies were diffuse large B-cell lymphoma (22 patients, 34%), T-cell lymphoma (15 patients, 23%), and Hodgkin lymphoma (13 patients, 20%). Most patients (81%) received BV treatment, and 17.2% received PV. Only one patient (1.6%) received both BV and PV. Forty-eight patients (75%) received other concurrent chemotherapies, among them were anti-PD-1 (3 patients, 4.7%), alkylating agent (8 patients, 13%), anti-CD20 (14 patients, 22%), anthracycline (21 patients, 33%), and anti-metabolite (2 patients, 3.1%). Overall, 40 patients (63%) experienced non-gastrointestinal toxicities associated with BV or PV treatment.

Figure 1.

Patient selection flowchart.

Table 1.

Patient characteristics (N = 64).

Characteristic	No. (%)
Median age, n (IQR), years	55 (42–70)
Sex
Male	32 (50)
Female	32 (50)
Race and ethnicity
White	44 (69)
Asian	5 (7.8)
Native Hawaiian/Pacific Islander	1 (1.6)
Black	10 (16)
Other	4 (6.3)
Median Charlson Comorbidity Index, n (IQR)	6 (4-9)
Cancer type
Hodgkin lymphoma	13 (20)
Diffuse large B-cell lymphoma	22 (34)
Systematic anaplastic large-cell lymphoma	8 (13)
Mantle cell lymphoma	1 (1.6)
T cell lymphoma	15 (23)
Other	5 (7.8)
Cancer treatment (BV or PV)
BV	52 (81)
PV	11 (17)
Combination BV/PV	1 (1.6)
Other concurrent cancer treatment
Anti-PD-1	3 (4.7)
Alkylating agent	8 (13)
Anti-CD20	14 (22)
Anthracycline	21 (33)
Anti-metabolite	2 (3.1)
Non-GI toxicities	40 (63)
Median duration of follow-up, n (IQR), years	0.8 (0.3–2.1)

BV, brentuximab vedotin; GI, gastrointestinal; IQR, interquartile range; PV, polatuzumab vedotin.

GI AE-related characteristics

The characteristics of patients’ GI AEs are presented in Table 2. The median duration of BV or PV therapy was 32 days, and the median duration between initiation of BV or PV therapy and GI AE onset was 37 days. Fifty patients experienced lower gastrointestinal tract toxicity (78%), and 29 patients experienced upper gastrointestinal tract toxicity (45%), 7 patients experienced hepatobiliary toxicity (11%), and 3 patients experienced pancreatic toxicity (4.7%). The most common symptoms on presentation were diarrhea (49 patients, 77%), nausea/vomiting (39 patients, 61%), and abdominal pain (33 patients, 52%). Of the 49 patients who experienced diarrhea, 11 patients (22%) experienced CTCAE grade 3 or 4 diarrhea. Of 37 patients who experienced colitis, only 1 patient (2.7%) experienced CTCAE grade 3 colitis, and no patients experienced grade 4 colitis. Of the 11 patients who were tested for fecal lactoferrin, 3 patients (27%) had a positive test result. Of the 10 patients who were tested for fecal calprotectin, 2 patients (20%) had a positive test.

Table 2.

GI AE-related characteristics (N = 64).

Characteristic	No. (%)
Median duration of BV or PV therapy, n (IQR), days	32 (1–105)
Median duration from BV or PV therapy initiation to GI AE onset, n (IQR), days	37 (10–97)
GI system involved
Upper GI^a	29 (45)
Lower GI^a	50 (78)
Hepatobiliary^a	7 (11)
Pancreas^a	3 (5)
Symptoms
Nausea and/or vomiting	39 (61)
Diarrhea	49 (77)
Constipation	9 (14)
Blood in stool (melena or hematochezia)	4 (6.3)
Abdominal pain	33 (52)
Diarrhea by CTCAE grade (n = 49)
1	13 (27)
2	25 (51)
3	8 (16)
4	3 (6.1)
Colitis by CTCAE grade (n = 37)
1	12 (32)
2	24 (65)
3	1 (2.7)
4	0 (0.0)
Positive lactoferrin (n = 11)	3 (27)
Positive calprotectin (n = 10)	2 (20)
Endoscopy performed	16 (26)
Endoscopic findings (n = 16)
Normal	5 (31)
Non-ulcerative inflammation	9 (56)
Ulcerative inflammation	2 (13)
Distribution of inflammation (n = 13)
Esophagus and/or stomach	7 (54)
Small intestine	5 (39)
Colon and/or rectum	6 (46)
Histopathological findings (n = 15)
Normal	6 (40)
Acute inflammation	6 (40)
Chronic inflammation	4 (27)
Cryptitis/apoptosis present	6 (40)

Twenty-five patients had both upper and lower GI AEs, two of whom had hepatobiliary toxicity, four had upper or lower GI accompanied by hepatobiliary toxicity, and one had hepatobiliary and pancreatic toxicity.

BV, brentuximab vedotin; CTCAE, Common Terminology Criteria for Adverse Events; GI AE, gastrointestinal adverse event; IQR, interquartile range; PV, polatuzumab vedotin.

GI AE endoscopy and histopathology findings

Overall, 16 (26%) patients underwent endoscopy, either upper or lower. Nine patients (56%) had non-ulcerative inflammation, and two patients (13%) had ulcerative inflammation. Of the 13 endoscopic evaluations that showed inflammation, 7 (54%) showed inflammation in the esophagus and/or stomach, 5 (39%) showed inflammation in the small bowel, and 6 (46%) showed inflammation in the colon and/or rectum. Some of these patients were noted to have inflammation in multiple segments of the gastrointestinal tract. Of the 15 biopsy samples taken for histopathological examination from all segments of the gastrointestinal tract, 6 samples (40%) showed acute inflammation and 4 samples (27%) showed chronic inflammation. Six samples (40%) also showed evidence of cryptitis and/or apoptosis.

GI AE therapy and outcomes

The patients’ GI AE therapy and outcomes are presented in Table 3. Fifty patients (78%) were hospitalized, and their median length of hospitalization was 15 days. Fifty-two patients (81%) were treated supportively, and three patients (4.7%) were treated with corticosteroids. The median symptom duration was 10 days, and the median treatment duration was 12 days. Of the 53 patients who received treatment, 49 patients (93%) had a treatment response or remission. Nineteen patients (37%) experienced symptom recurrence after completion of treatment, and eight patients (13%) experienced complications as a result of gastrointestinal toxicity, including six patients who had chronic colitis, defined as a course of colitis persisting beyond 4 weeks, and two patients who had gastrointestinal infections. Twenty-six patients (41%) stopped their BV or PV therapy due to GI AE. No patients died as a result of GI AE; however, the all-cause mortality rate at the time of data collection was 44%.

Table 3.

GI AE treatment and outcomes (N = 64).

Characteristic	No. (%)
Treatment received
Supportive	52 (81)
Corticosteroids	3 (4.7)
Median duration of symptoms from GI AE diagnosis until response or remission achieved, n (IQR), days	10 (5–22)
Median duration of GI AE treatment, n (IQR), days	12 (6–23)
GI AE treatment response or remission achieved (n = 53)	49 (93)
Patients requiring hospitalization	50 (78)
Median duration of hospitalization, n (IQR), days	15 (6–23)
Symptom recurrence	19 (37)
GI AE complications^a	8 (13)
PV or BV therapy stopped for GI AE	26 (41)
All-cause mortality	28 (44)

Complications include chronic colitis (six patients) and GI infection (two patients).

BV, brentuximab vedotin; GI AE, gastrointestinal adverse event; IQR, interquartile range; PV, polatuzumab vedotin.

Comparative analysis of GI AE characteristics, treatment, and outcomes by cancer therapy

A comparison of GI AE characteristics, treatment, and outcomes by cancer therapy received (BV vs PV) is presented in Table 4. We found no significant differences in the endoscopic findings, histopathological findings, or the characteristics of treatments and outcomes between patients who received BV and those who received PV.

Table 4.

Comparison of GI AE characteristics, treatment, and outcomes by cancer therapy (N = 64).

Characteristic	BV(n = 52)	PV(n = 12)	p Value
Median duration of BV/PV therapy, n (IQR), days	32 (1–107)	21 (1–69)	0.477
Median duration from BV/PV therapy initiation to GI AE onset, n (IQR), days	36 (8–102)	37 (20–59)	0.854
GI system involved
Upper GI	23 (44%)	6 (50%)	0.741
Lower GI	47 (90%)	9 (75%)	0.595
Hepatobiliary	3 (5.8%)	2 (17%)	0.207
Pancreas	3 (5.8%)	0 (0.0%)	1.000
Symptoms
Nausea/vomiting	31 (60%)	7 (58%)	1.000
Diarrhea	41 (79%)	8 (67%)	0.696
Constipation	7 (14%)	2 (17%)	1.000
Blood in stool (melena or hematochezia)	2 (3.8%)	2 (17%)	0.137
Abdominal pain	27 (52%)	6 (50%)	1.000
Median duration of symptoms from GI AE diagnosis until response or remission achieved, n (IQR), days	10 (6–21.5)	12 (4–15)	0.924
Diarrhea by CTCAE grade (N = 49)			0.343
1	11 (27%)	2 (25%)
2	22 (54%)	3 (38%)
3	5 (12%)	3 (38%)
4	3 (7.3%)	0 (0.0%)
Colitis by CTCAE grade (N = 37)			1.000
1	9 (31%)	3 (38%)
2	19 (64%)	5 (63%)
3	1 (4.4%)	0 (0.0%)
4	0 (0.0%)	0 (0.0%)
Positive lactoferrin (N = 11)	3 (30%)	0 (0.0%)	1.000
Positive calprotectin (N = 10)	2 (22%)	0 (0.0%)	1.000
Endoscopy performed	13 (26%)	3 (25%)	1.000
Distribution of inflammation (N = 13)
Esophagus and/or stomach	7 (64%)	0 (0.0%)	0.192
Small intestine	4 (36%)	1 (50%)	1.000
Colon and/or rectum	4 (36%)	2 (100%)	0.192
Endoscopic findings (N = 16)			1.000
Normal	4 (31%)	1 (33%)
Non-ulcerative inflammation	7 (54%)	2 (67%)
Ulcerative inflammation	2 (15%)	0 (0.0%)
Histopathological findings (N = 15)			1.000
Normal	5 (39%)	1 (50%)
Acute inflammation	5 (39%)	1 (50%)
Chronic inflammation	4 (31%)	0 (0.0%)
Treatment
Supportive	42 (81%)	9 (75%)	1.000
Corticosteroids	3 (5.8%)	0 (0.0%)	1.000
Median duration of GI AE treatment, n (IQR), days	10 (6–23)	14 (12–16)	0.339
GI AE treatment response or remission achieved (N = 53)	41 (95%)	7 (78%)	0.134
Patients requiring hospitalization	40 (77%)	10 (83%)	0.433
Median duration of hospitalization, n (IQR), days	13 (6–22)	18.5 (12–26)	0.297
Symptom recurrence	17 (41%)	2 (17%)	0.455
GI AE complications^a	7 (13%)	1 (8.3%)	0.750
Agent stopped for GI AE	20 (39%)	6 (50%)	0.339
All-cause mortality	22 (42%)	5 (42%)	1.000

Complications include chronic colitis (six patients) and GI infection (two patients).

BV, brentuximab vedotin; CTCAE, Common Terminology Criteria for Adverse Events; GI AE, gastrointestinal adverse event; IQR, interquartile range; PV, polatuzumab vedotin.

Discussion

GI AEs occurring after the use of targeted antibody–drug conjugates such as BV and PV have been reported in prior clinical trials and case reports.^4–10 However, the clinical presentation and treatment of these GI AEs have not yet been characterized in a cohort study. As the use of these and other targeted cancer therapies has expanded, GI AEs have been increasingly recognized as significant barriers to effective cancer treatment.^1,2,15–18 Here, we presented a retrospective cohort study of patients who developed GI AEs following BV or PV therapy and described the clinical characteristics, disease course, and therapeutic management of these drug-induced gastrointestinal toxicities.

The clinical presentations of GI AE after BV and PV therapy in our cohort were varied, with common gastrointestinal presentations, such as diarrhea, nausea/vomiting, abdominal pain, and constipation, which are consistent with prior reports.^3–10 We also observed hepatobiliary and pancreatic toxicity, which has also been previously reported in case reports.^19–25 In general, the presentation of these GI AEs was subacute and mild in severity, with most classified as CTCAE grades 1 or 2. We noted 49 patients who experienced mild diarrhea and 37 patients who experienced low grades of colitis. This finding is similar to reports in prior clinical trials that described a low incidence of high-grade diarrhea.^4–7 Furthermore, we excluded patients who had previously received ICIs or stem cell transplantation to avoid cases with confounding inciting agents. However, notably, many of our patients received multi-drug regimens, which makes clearly delineating the inciting agent a challenging task.

In our study, only a small proportion of patients underwent endoscopy, in accordance with the mild symptoms seen in our cohort. Most of these patients had findings of normal mucosa or non-ulcerative inflammation. Many of the biopsy samples had acute inflammation with evidence of crypt architectural distortion, inflammation, or apoptosis. Prior case reports of BV-induced colitis have described similar endoscopic findings of both non-ulcerative and ulcerative inflammation with histopathological findings of neutrophilic infiltration, atrophic cryptitis, and prominent apoptotic bodies.^8–10 Other studies have revealed similar histopathological patterns of cryptitis and apoptosis in colitis related to other drugs, such as ICIs, mycophenolate, 5-fluorouracil, the phosphoinositide 3-kinase-d inhibitor idelalisib, and anti-tumor necrosis factor antibodies.^26–30 In the case of ICI-mediated colitis, decreased regulation of autoreactive CD8 T cells could lead to autoimmunity, resulting in immune-related AEs.²⁶ However, the mechanisms by which BV and PV can cause colonic inflammation are unclear.

BV consists of a CD30-specific monoclonal antibody that targets a cell-surface antigen on Reed-Sternberg cells in classic Hodgkin lymphoma, whereas PV consists of a CD79b-specific monoclonal antibody that targets a B-cell antigen receptor involved in cell signaling that is expressed on mature B-cell lymphomas.^5–7 Both BV and PV are antibody–drug conjugates that are conjugated by a protease-cleavable linker to the microtubule-disrupting agent monomethyl auristatin E.^5–7 It is unclear if similar manifestations of autoimmunity can be induced by CD30-specific or CD79b-specific inhibition. Previously, it was hypothesized that antibody–drug conjugates may cause gastrointestinal toxicity through the action of microtubule inhibitors on rapidly proliferating cells in the gastrointestinal tract.^31,32 Other chemotherapeutic drugs that disrupt microtubule function, such as taxanes, have been observed to cause colitis presenting with endoscopic evidence of significant inflammation or as microscopic colitis.³³ Prior experiments showed ACF7, a protein that facilitates microtubule organization, to be important in intestinal wound healing in vitro due to its contribution to tight junction stabilization, and the loss of this protein in vivo was found to cause inhibition of intestinal wound healing and greatly increase susceptibility to experimental colitis in mice.³⁴ Therefore, it is possible that BV and PV may also induce gastrointestinal inflammation through similar mechanisms of microtubule dysfunction. Interestingly, CD30 and CD79b are not normally expressed in normal colonic epithelium but are implicated in immune regulation in certain colonic disease states in the setting of immune cell infiltration.^35–37 Further research in these areas may be helpful in understanding the mechanism behind these toxicities.

In our study, a few patients were evaluated for markers of colonic inflammation, such as fecal lactoferrin and calprotectin. Overall, only a small proportion of tested patients had positive results. While evidence supporting the use of these markers is most established in inflammatory bowel disease, recent work has highlighted the utility of calprotectin in the evaluation of ICI-mediated colitis.³⁸ In that study, fecal calprotectin was effective in predicting remission of colitis as determined by endoscopy and histology in patients receiving treatment for ICI-mediated colitis. In our small cohort, none of the five patients who had positive calprotectin or lactoferrin test results received corticosteroid therapy, suggesting that these markers may not be as effective in predicting disease severity and the need for immunosuppressive therapy in these patients. Larger-scale studies may help clarify the role of these inflammatory markers in evaluating for BV- or PV-induced colitis.

Most of our patients received only supportive care for their symptoms. Only a few patients required corticosteroids to achieve symptom improvement and remission, although many patients did have symptom recurrence and discontinued the targeted antibody–drug conjugate therapy, likely due to GI AE. Furthermore, most patients were hospitalized, which should be further explored as the data suggest that patients had a mild clinical course. The optimal management of GI AEs secondary to BV or PV therapy remains unestablished. In general, the standard management of chemotherapy-induced diarrhea is supportive with anti-diarrheal agents, such as loperamide, and rarely, the use of alternative agents, such as octreotide, is necessary.^39–42 The current standard of care for moderate-to-severe ICI-mediated colitis is treatment with 4–6 weeks of corticosteroids with consideration of selective immunosuppressive therapy, such as infliximab or vedolizumab.^43–47 Early use of selective immunosuppressive therapy has been shown to improve the outcomes of patients with ICI-mediated colitis.⁴⁷ Corticosteroids and other immunosuppressive agents have also been proposed as therapies for ICI-mediated hepatobiliary and pancreatic toxicities.^45,48,49 Future research may help elucidate whether early diagnosis and use of immunosuppressive therapy can reduce rates of GI AE-related hospitalization, recurrence, and the need for cancer therapy discontinuation.

Our study has certain limitations. First, because we performed a retrospective cohort study of single-center data with a limited sample size and a highly selected patient population, there were risks of selection biases. As an example, we strictly excluded patients who had studies that indicated alternative causes of their symptoms and patients who carried other chronic gastrointestinal disease diagnoses. This may have led to the differences seen in the prevalence of GI AE when compared to prior clinical trials that included these patients.^3–7,50 Furthermore, there was a limited number of patients in our study who received PV, and therefore our analysis was underpowered to fully compare the differences between the two agent groups. In addition, our population of patients with hepatobiliary or pancreatic toxicity was small, leading to limited analysis of these topics. Although we graded AEs strictly based on criteria defined by the National Cancer Institute’s CTCAE, Version 5.0, grading AEs retrospectively is challenging and may introduce potential inherent biases. We also acknowledge that concurrent cancer therapies may also pose a risk of gastrointestinal toxicity that is difficult to delineate from the BV/PV AEs. Lastly, one patient in our cohort had an absolute neutrophil count in the neutropenic range, which also can lead to neutropenic colitis with overlapping symptom.

Conclusion

Post-therapy GI AEs associated with BV and PV may affect various systems of the gastrointestinal tract, including the upper and lower gastrointestinal tracts, hepatobiliary system, and pancreatic system. We observed a subacute presentation in most patients, with a few patients who developed high grades of diarrhea and colitis or ulcerative inflammation on endoscopy. Most patients had remission through supportive care, with only a few needing corticosteroids. However, a substantial proportion of patients had to discontinue BV or PV therapy due to GI AEs, and these patients had a considerable recurrence rate. Future large-scale studies are still warranted to provide further clarification on the disease course and the impact of different treatment options on clinical outcomes.

Supplemental Material

sj-docx-1-tam-10.1177_17588359261417635 – Supplemental material for Gastrointestinal adverse events following brentuximab vedotin and polatuzumab vedotin therapy

Supplemental material, sj-docx-1-tam-10.1177_17588359261417635 for Gastrointestinal adverse events following brentuximab vedotin and polatuzumab vedotin therapy by Andrew G. Kuang, Malek Shatila, Jay S. Shah, Nitish Mittal, Sidra Naz, Ugochi Ebinama, Swaminathan P. Iyer, Paolo Strati, Mehnaz A. Shafi, Anusha S. Thomas, Hao Chi Zhang and Yinghong Wang in Therapeutic Advances in Medical Oncology

Footnotes

Acknowledgements

Medical editing of this paper was provided by Ashli Nguyen-Villarreal in the Research Medical Library at The University of Texas MD Anderson Cancer Center.

Declarations

ORCID iD

Yinghong Wang

Supplemental material

Supplemental material for this article is available online.

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