CASE REVIEW

A local case report of relapsed/refractory hodgkin lymphoma: A positive outcome with brentuximab vedotin

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Dr. Mak, Wai-Man, Vivien

Specialist in Hematology

Most of the Hodgkin lymphoma (HL) patients respond well to frontline treatment, but such treatments induce unacceptable organ toxicities and immune suppression, which leads to secondary malignancies and cardiac disease.1 Therefore, increased interest has drawn towards targeted immunotherapies to provide effective treatment with higher safety profile.1 Brentuximab vedotin has shown positive outcomes in the management of relapsed and refractory cases of HL.1 In this case review, Dr. Vivien Mak presented a case of a lady with relapsed/refractory HL, who was presented with a mediastinal mass, and resistant to standard regimens of chemotherapy. She responded astonishingly well to monotherapy with brentuximab vedotin and is currently on her way to complete recovery.

Background

Hodgkin lymphoma (HL) is a B-cell-derived malignancy, which represents 10% of all lymphomas.1 In USA, 8,500 new cases and 1,050 deaths were registered in 2018.1 More than 80% of patients with HL have intrathoracic involvement at the initial presentation.2 In the thorax, HL most frequently involves the superior mediastinal and paratracheal regions.2 The management has been drastically improved among relapsed/refractory HL with the frontline regimens and the ten-year survival rate is estimated to be 75%.3

The most commonly used frontline regimens for HL are ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) and BEACOPP (bleomycin, etoposide, doxorubicin hydrochloride, cyclophosphamide, vincristine, procarbazine and prednisone), where more patients were reportedly relapsed with ABVD.4 As significant long term toxicities are observed with conventional therapies, recent advancement of immunotherapy in the treatment of HL has marked a new era.1 Brentuximab vedotin is an antibody-drug conjugate which targets CD30 on tumor cells.5 By delivering an antineoplastic agent, it induces apoptotic cell death in CD30-expressing tumor cells.5,6 As CD30 is associated with high density in tumor cells of patients with relapsed/refractory HL, brentuximab vedotin has shown promising effects in the recovery of these patients.5,6

Case report

The present case is a 34-year-old lady who was a chronic smoker and a heavy drinker, presented with signs of obstruction of superior vena cava (SVC). She also had clinical features of myasthenia gravis with neurologically confirmed proximal muscle weakness, but negative acetylcholine receptor antibody expression. Furthermore, an electromyography showed diagnostic features of myasthenia gravis. Subsequently, a chest radiograph had discovered an extensive mediastinal mass. In the PET scan, the dimensions of the heterogenous soft tissue mass was 7.8 x 17.8 x 9.7cm, encasing brachiocephalic vein, brachiocephalic truck, the common carotid artery, the aorta, and SVC. A short segment of SVC narrowing was also observed due to the tumor infiltration. A right cervical lymph node biopsy revealed nodular sclerosis classical HL. In May 2017, the HL was classified as stage II, unfavorable, with a large mass and elevated ESR.

Standard ABVD regimen was immediately initiated and after three cycles, PET scan was performed. Subsequently, a persistent lesion was observed with tumor size of 11.6 x 3.9 x 9.6cm and SUV of 7.8. Although, more intensive treatment with escalated BEACOPP was proposed to the patient at this juncture, she refused because of in-patient setting. Hence, there was no choice, but to continue ABVD up to 6 cycles and the PET scan done later revealed a tumor with slight reduction in size but is still highly metabolic active. Then the treatment was delayed, because the patient needs a gynecology operation. In April 2018, CT scan restaging discovered the size of the tumor as 17.0 x 8.8cm. Another biopsy was done to confirm the diagnosis as the tumor was not responsive to the treatment and a differential diagnosis of thymoma was suspected. The biopsy results confirmed the initial nodular sclerosis classical HL diagnosis. As the patient became more cooperative, the treatment regimen was changed to DHAP (dexamethasone, cytarabine and cisplatin) for three courses as part of the standard treatment. After three months, a PET scan depicted a persisting mass of 9.8 x 1.4 x 10cm with a SUV of 18.3.

Afterwards, in August 2018, she was given monotherapy with brentuximab vedotin for four cycles. A PET scan performed in October 2018 revealed that the lesion was resolved both metabolically and anatomically leaving only a patchy consolidated area with a SUV of 3.8. With the positive response to brentuximab vedotin, an ASCT was planned. Because of the waiting time, the patient was given another three cycles of brentuximab vedotin before harvesting autologous stem cells. As adequate yield of stem cells was harvested, ASCT was carried out in March 2019. She tolerated the conditioning regimen (BEAM: Carmustine, Etoposide, Cytarabine and Melphalan) well and engrafted successfully.

Discussion

In the phase 2 trial, the efficacy and safety of brentuximab vedotin were evaluated on patients with relapsed or refractory HL (n=102).7 The objective response rate (ORR) was 75% with complete remission (CR) in 34% of patients.7 The median progression-free survival (PFS) time for all patients was 5.6 months, and the median duration of response for those in CR was 20.5 months.7 As shown in Figure 1, drastic reductions in tumor size was observed in 94% of patients.7 In the follow up study of this phase 2 trial, had estimated 5-year overall survival (OS) rate of 41% and PFS rate of 22%.8 The time durations for OS and PFS were 40.5 months and 9.3 months.8 Furthermore, they have reported 9% of the enrolled population achieving long-term remission exceeding 5 years as a response to monotherapy with brentuximab vedotin.8 Recently, a retrospective multicenter study confirmed the findings of brentuximab vedotin as an effective treatment for relapsed/refractory HL patients with an ORR of 60%.9 Within this study, the PFS time was 8 months and OS time was 26.5 months.9

The patient described in the current case endured the brentuximab vedotin well, as it was according to her wish, an outpatient therapy, thus her quality of life improved. With the positive outcomes of brentuximab vedotin, patient’s prospective towards the treatment has completely altered and she is more receptive on current therapies. The PET scan will be repeated at three months after the transplant. We are planning to give brentuximab vedotin consolidation to the patient.

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Conclusion

This is a remarkable case of a HL patient with a progressive tumor which is resilient to conventional chemotherapy. The patient responded to brentuximab vedotin monotherapy positively, which allowed her to undergo ASCT. Considering the present case, Dr. Mak commented, “Treatment with brentuximab vedotin is beneficial even in patients who have progressive disease despite two lines of therapy.”

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