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M.J. Kersten et al.
Table 2. Adverse events grade 3 or 4 during brentuximab vedotin and dexamethasone, high-dose cytarabine and cisplatin, high-dose cytarabine, cisplatin.
Cycle 1 Cycle 2 Cycle 3 Total* Adverse event (n=55) (n=53) (n=51) (n=55)
CTCAEgrade(n) 34343434
Febrile neutropenia Elevated liver enzymes Electrolyte disorders Nausea/vomiting Fever
Renal function disorder Sepsis
Bone pain
Diarrhea
Epistaxis
Infection
Infusion-related reaction Malaise
Abdominal pain
Back pain
Constipation
Headache
Myalgia shoulder
Periodic paralysis (hypokalemia) Syncope
Total
Individual patients†
Individual patients total‡
7 1 2 3 0 5 2 1 0 1 0 3 0 0 1 1 0 0 0 0 1 2 0 0 1 0 1 0 0 1 0 0 1 0 0 2 1 0 1 1 0 0 0 0 0 0 0 0 1 0 0 1 0 0 1 0 0 0 0 0
0 3 1 1 1 2 0 2 0 2 0 2 1 1 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 1
1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
12 (22%) 9 (16%) 4 (7%) 4 (7%) 3 (5%) 3 (5%) 2 (4%) 2 (4%) 2 (4%) 2 (4%) 2 (4%) 2 (4%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%) 1 (2%)
2 (4%) 1 (2%) 2 (4%) 0 (0%) 0 (0%) 0 (0%) 1 (2%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%) 0 (0%)
22 2 18 3 18 1
55 6
29 5
30 (55%)
17
2 14
2 11
1
18 (33%)
15 (28%)
11 (22%)
*Patients with a specific toxicity in more than one cycle were only counted once in the column representing the total toxicity. †Total of patients who experienced one or more grade 3 or 4 toxicity during the cycle concerned. ‡Total of patients who experienced one or more grade 3 or 4 toxicity during the cycle concerned. Patients who experienced both a grade 3 and grade 4 toxicity were only counted once. n: number; CTCAE: Common Terminology Criteria for Adverse Events.
A sequential approach of BV monotherapy followed by chemotherapy in PET-positive patients is interesting, since some patients could be spared the toxicity of salvage chemotherapy without losing efficacy. However, only a minority of patients achieved a PET-negative response after BV monotherapy.15 The ESHAP regimen is similar to DHAP, except that it contains methylprednisolone instead of dexamethasone, and cisplatin is given over 4 days of 25 mg/m2/day compared to 100 mg/m2 in one day with the DHAP regimen.18 Hematologic toxicity was comparable between BV-ESHAP and BV-DHAP with about 50% of patients experiencing grade 3/4 thrombocytopenia and neutropenia. For BV-ESHAP, grade 3 fever and mucositis were the most frequent non-hematologic grade 3/4 toxic- ities whereas DHAP was also associated with fever, but not with mucositis. In contrast, only grade 1/2 renal dys- function occurred with BV-ESHAP, and no cases of elevat- ed liver enzymes or ototoxicity are described.18
In ten patients, a transient grade 3/4 increase in liver enzymes was observed during BV-DHAP treatment (n=1 grade 4), which was reversible in all patients. One patient developed a fatal VOD after BEAM/auto-PBSCT. Additionally, one patient treated in the phase I part of this study also developed a grade 3 VOD, which, however, recovered without sequelae. Both patients already had elevated liver enzymes during BV-DHAP treatment. This complication has previously been described in patients
receiving high-dose alkylating agents such as melphalan or cyclophosphamide.35
BV as consolidation therapy has been shown to prolong PFS in high-risk R/R cHL patients who have undergone HDC/auto-PBSCT.36 Whether BV before auto-PBSCT in combination with chemotherapy, or as consolidation after auto-PBSCT will be more effective is unknown. Of note, with BV consolidation, peripheral neuropathy occurred in 67% of patients, including 13% (n=22) grade 3 peripheral neuropathy. With BV-DHAP, the incidence of peripheral neuropathy was lower, was mostly reversible, and no grade 3/4 occurred, probably because only three adminis- trations of BV were given.
In-depth pathology workup and reclassification were performed to exclude lymphomas that are known as cHL mimickers such as AITL and PTCL (with follicular helper T-cell immunophenotype with secondary cHL-like blasts), as well as immunodeficiency-associated B-cell lympho- proliferative disorders (IA-B-LPD).37-39 In retrospect, seven cases were identified as cHL-mimickers with central pathology review. Awareness for cHL-mimickers is impor- tant because patients with T-cell lymphoma generally have a worse prognosis.40 In this cohort of patients, no sig- nificant differences in response rates or PFS were observed between patients with confirmed or unconfirmed cHL, although the number of patients is too small to validate this finding.
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