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EHA 2019 | Two-year follow-up of CheckMate 205: nivolumab plus doxorubicin, vinblastine, and dacarbazine in newly diagnosed advanced-stage cHL

On Saturday, 15 June 2019, during the 24th Congress of the European Hematology Association (EHA) in Amsterdam, NL, Eva Domingo-Domènech, from the Institut Catala d’Oncologia, Barcelona, ES, discussed the results of a phase II study (NCT02181738; CheckMate 205) in patients with newly diagnosed, previously untreated classical Hodgkin lymphoma (cHL). During this trial, patient cohort D received multi-agent chemotherapy with nivolumab, doxorubicin, vinblastine, and dacarbazine (N-AVD).1

Current multi-agent chemotherapy regimens lead to suboptimal results in newly diagnosed patients with advanced-stage cHL. However, the use of nivolumab, an anti–PD-1 checkpoint inhibitor, followed by N-AVD has shown promising activity in this patient population, as indicated by the 9-month follow-up of the CheckMate 205 that was presented last year at EHA.2 This year, Dr Domingo-Domènech provided an update on the study results after a 2-year follow-up of the patient cohort.

Study design
  • Patients received monotherapy with nivolumab (four doses; 240mg intravenously every two weeks) for approximately eight weeks, followed by N-AVD combination therapy (12 doses) for approximately 22 weeks
  • 49 out of 51 patients (96%) completed monotherapy and 45/50 (90%) completed N-AVD combination therapy
  • Median follow-up was 25.3 months (n=48)

Table 1. Patient characteristics.

Characteristics

Newly diagnosed cHL

(N=51)

Median age (range), years

37 (18–87)

Male patients

32 (63%)

International Prognostic Score at diagnosis

0–1

2–3

≥4

Not reported

 

12 (24%)

21 (41%)

13 (25%)

5 (10%)

Disease stage at diagnosis

II

III

IV

 

10 (20%)

12 (24%)

29 (57%)

B symptoms at diagnosis

41 (80%)

Bulky disease

16 (31%)

Extranodal involvement

25 (49%)

Key findings
  • Progression-free survival (PFS) at 21 months by investigator assessment was 83% (95% CI, 69–91)
  • Combination therapy improved response rates, with the majority of patients achieving complete response (CR) or complete metabolic response (CMR) at the end of therapy (see table below)

Table 2. Responses in the intention-to-treat (ITT) population.

Response rate* (%)

End of monotherapy

 

After two combination cycles

End of therapy

IRC

ORR

71

90

86

CR

18

51

69

PR

53

39

18

Investigator

ORR

67

88

84

CR

25

71

80

PR

41

18

4

IRC-Deauville

ORR

88

84

76

CMR

18

71

75

PMR

71

14

2

*, values may not total ORR due to rounding; ORR, objective response rate; CMR, complete metabolic response (Deauville ≤3); IRC, independent review committee; PMR, partial metabolic response

 Safety
  • Two patients died after the last dose of N-AVD
    • One patient (68 years old), treated for 175 days, died 38 days after the last dose due to the study drug toxicity (acute respiratory failure)
    • One patient (85 years old), treated for 209 days, died 451 days after the last dose due to disease progression

Table 3. Treatment-related adverse events (AEs).

Treatment-related AEs in ITT population

Any grade, n (%)

Grade 3–4, n (%)

Total patients with treatment-related AEs

49 (96)

30 (59)

Immune-mediated

Rash

Increased alanine aminotransferase

Increased aspartate aminotransferase

Infusion-related reaction

Pneumonitis

 

3 (6)

2 (4)

1 (2)

2 (4)

1 (2)

 

0

2 (4)

1 (2)

0

0

Hematologic/investigations ( 5% patients)

Neutropenia

Decreased white blood cell count

Decreased neutrophil count

Febrile neutropenia

Increased alanine aminotransferase

Anemia

Increased amylase

 

24 (47)

7 (14)

6 (12)

5 (10)

4 (8)

4 (8)

3 (6)

 

21 (41)

1 (2)

6 (12)

5 (10)

2 (4)

1 (2)

0

All others (≥ 10% patients)

Nausea

Infusion-related reaction

Fatigue

Pyrexia

Constipation

Hypothyroidism

Vomiting

Arthralgia

Stomatitis

 

18 (35)

16 (31)

13 (25)

7 (14)

7 (14)

7 (14)

7 (14)

6 (12)

6 (12)

 

1 (2)

0

0

1 (2)

0

0

0

0

0

Conclusion

Nivolumab followed by N-AVD offered benefit to patients with newly diagnosed, advanced stage cHL, leading to high ORR (86%) and CMR (75%), as well as prolonged PFS (83% at 21 months). The therapy was also well tolerated. Dr Domingo-Domènech concluded that this treatment strategy may be a promising alternative to the current standard of care for newly diagnosed, previously untreated patients with advanced-stage cHL.

References
  1. Domingo-Domènech E. et al., Nivolumab plus doxorubicin, vinblastine and dacarbazine for newly diagnosed advanced-stage classical Hodgkin lymphoma: 2-year extended follow-up from cohort D of the phase 2 CheckMate 205 study; 2019. Abstract #S821: 24th EHA Congress, Amsterdam, NL
  2. Ramchandren R. et al., CHECKMATE 205 cohort D: a phase 2 trial of nivolumab for newly diagnosed advanced-stage classical Hodgkin lymphoma; 2018. Abstract #S114: 23th EHA Congress, Stockholm, SE

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