Hodgkin’s Disease: Drug Therapy

Therapeutic targets

Complete remission (complete tumor regression).
Healing

Therapy recommendations

The main component of therapy for Hodgkin’s disease is polychemotherapy.
Combined chemoradiation therapy should be given as primary therapy in patients with early-stage Hodgkin lymphoma.
See also under “Other therapy.”

Primary therapy is carried out with [S3 guideline]:

Early stage:
- Age < 60 years: ABVD (adriamycin, bleomycin, vinblastine, dacarbazine; two cycles,followed by involved-field (IF) radiotherapy with a radiation dose of 20 Gy
- Age > 60 years (affects approximately 20% of all Hodgkin’s disease patients): 2 cycles of ABVD followed by 20 Gy involved-site radiotherapy.
- Note: PET/CT after 2 cycles of ABVD can be performed as an individual decision – e.g., in young patients – and in the case of a negative PET/CT, the benefit of consolidative radiotherapy should be weighed against the potential secondary malignancy risk.In the case of a positive PET/CT, therapy intensification in the form of two additional cycles of chemotherapy BEACOPPescalated should be considered.
Intermediate stage (intermediate stage): a total of 4 cycles of polychemotherapy should be administered:
- Age ≤ 60 years: BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), two cycles, followed by two cycles of ABVD [CI in patients > 60 years]; alternatively, PET-adapted strategy, increasing to two cycles of BEACOPP esk after 2 cycles of ABVD in case of PET-positive residuals [see “Further guidance” below].
  - In case of contraindication (contraindications) or refusal of BEACOPPescalated, chemotherapy consisting of 4 cycles of ABVD (or 2 cycles of ABVD + 2 cycles of AVD in patients >60 years of age) should be chosen as the next best option.
  - After chemotherapy with 2 cycles of BEACOPPescalated followed by 2 cycles of ABVD (“2+2”), consolidative RT with a dose of 30 Gy should be applied.
- Age > 60 years: 2 cycles of ABVD followed by 2 cycles of AVD and 30 Gy involved-site radiotherapy. BEACOPP should not be used in this patient population.
Advanced stage:
- Age < 60 years: BEACOPP esk,
  - The number of cycles is based on the result of interim staging by PET/CT after 2 cycles.
    - PET/CT-negative patients should receive 2 additional cycles of BEACOPPescalated,
    - PET/CT-positive patients are to receive 4 additional cycles, as before.
- Brentuximab vedotin (BV; dosing of 1.8 mg/kg body weight) for first-line therapy in adults with previously untreated advanced stage IV Hodgkin lymphoma in combination with AVD (doxorubicin (Adriamycin), vinblastine, dacarbazine).
- Alternative: nivolumab (checkpoint inhibitor: blockade of immune checkpoint PD-1): four doses of nivolumab monotherapy followed by twelve doses of nivolumab AVD (adriamycin, vinblastine, dacarbazine).
Note the following specifics (age, sex):
- Presence of risk factors (age > 40 years or reduced general condition): administration of a pre-phase to further reduce TRM (“treatment-related mortality”).
- Women of reproductive age: ovarian protection (“protection of the ovaries“) by prophylactic permanent prescription of a hormonal contraceptive (“pill”) or administration of GnRH analogues (GnRH: gonadotropin-releasing hormone).
- Cryopreservation (see below “Further therapy”).
No information on dosages is given here, as there are often changes in the respective regimens during chemotherapy.

Further notes

For advanced stage, omission of radiotherapy of PET-negative tissue remnants after completion of chemotherapy is established.
HD18 study of the German Hodgkin Study Group in patients with advanced stage lymphoma disease: in patients with advanced Hodgkin’s disease and positive PET results, the number of chemotherapy cycles can be reduced without loss of efficacy. Six cycles of BEACOPP is enough. The therapy regimen (BEACOPP-escalated) includes bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone.Similarly, reducing the number of cycles from eight or six to four did not result in a worse treatment outcome in patients in whom the PET result was negative Five years after the start of the study, overall survival according to intention-to-treat (ITT) analysis was
- 95.4% (95% confidence interval: 93.4-97.3) when patients received eight or six BEACOPP cycles
- 97.6% (95% confidence interval: 96.0-99.2) when the number of cycles was limited to four.
The difference of 2.2% is significant: (hazard ratio: 0.36 [95% confidence interval: 0.17-0.76; p = 0.006]).

Recurrent Therapy

Until the age of 60 years: High-dose chemotherapy with autologous stem cell transplantation (stem cells by self-donation).
- Patients over 60 years of age in good physical condition and without severe concomitant disease may receive high-dose chemotherapy with autologous stem cell transplantation for relapse or progression of Hodgkin lymphoma [S3 guideline].
If stem cell transplantation cannot be performed, the patient should be treated with palliative antibody therapy with brentuximab vedotin (anti-CD30 antibody plus cystostatic), chemotherapy, or radiotherapy (radiatio).
In case of relapse after autologous stem cell transplantation (auto-SCT), patients with a good general condition can receive an allogeneic stem cell transplant (stem cells from related or unrelated donors), after a dose-reduced (nonmyeloablative) conditioning; alternatively, a relapse (recurrence of the disease), a new autologous stem cell transplant can be performed.
After failure of autologous stem cell therapy (auto-SCT):
- Brentuximab vedotin (BV; dosage of 1.8 mg/kg body weight) can still achieve long-term remissions. The most common side effect of immunotoxin therapy was peripheral neuropathy. This had completely disappeared or had significantly improved in most patients (88%) by the end of the study.
- Pembrolizumab (PD-1 (programmed cell death 1 protein) inhibitor) monotherapy (200 mg every 3 weeks until cancer progression, or unacceptable toxicity) for