Division of Hematologic Malignancies and.
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA.
Blood Adv. 2021 Mar 23;5(6):1648-1659. doi: 10.1182/bloodadvances.2020003556.
Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.
自体干细胞移植(ASCT)可治愈复发/难治性霍奇金淋巴瘤(HL)患者。基于研究表明抗 PD-1 单克隆抗体(mAb)可使患者对后续化疗敏感,我们假设在 ASCT 前接受抗 PD-1 治疗会使在≥1 种挽救方案上进展或反应不足的高危患者(包括传统上被认为是 ASCT 不良候选者的化疗耐药患者)获得可接受的结果。我们回顾性地确定了 78 例在 22 个中心接受 ASCT 的 HL 患者,这些患者在接受抗 PD-1 mAb(单独或联合)作为三线或更晚的治疗后进展。化疗耐药疾病很常见,包括 42 例(54%)在接受抗 PD-1 治疗前立即对≥2 种连续系统治疗耐药。58 例(74%)患者在抗 PD-1 治疗后进行 ASCT,而 20 例(26%)患者在 PD-1 阻断后并在 ASCT 前接受了额外的治疗。患者在 ASCT 前接受了中位数为 4 种系统治疗(范围 3-7),31 例(41%)患者在 ASCT 前有阳性正电子发射断层扫描(PET)结果。在 ASCT 后中位随访 19.6 个月后,18 个月无进展生存率(PFS)和总生存率分别为 81%(95%CI,69-89)和 96%(95%置信区间[CI],87-99)。在 PD-1 阻断前连续 2 种治疗耐药的患者(18 个月 PFS,78%)、ASCT 前有阳性 PET(18 个月 PFS,75%)或接受≥4 种系统治疗的患者(18 个月 PFS,73%)观察到有利的结果,而 PD-1 无应答者的结局较差(18 个月 PFS,51%)。在这个高危患者队列中,ASCT 后接受抗 PD-1 治疗与优异的结果相关,甚至在接受过大量预处理、先前化疗耐药的患者中也是如此。