Contributions
Abstract: PB2228
Type: Publication Only
Background
The anti-CD38+ monoclonal antibody Daratumumab (dara) is established as part of the treatment pathway for MM, along with autologous stem cell transplantation (ASCT) (IMWG 2017). Patients who have previously received, or are receiving Daratumumab have altered cellular inmmunological status (ASH 2017 abstract 3148)
Aims
To review suppression of normal serum immunoglogulins in dara treated patients, and possible increased infection risk (EBMT 2018 Powles et al Abstract B232), and whether this impinges on the safety of ASCT. To determine if in ASCT patients, this altered immune status, results in poor stem cell harvesting, delayed engraftment, infections, possible autologous GVHD, and dara infusion- related reactions when re-challenged post ASCT. We also look to see if suppression of normal Free Light Chain (FLC) levels occurs on dara, which may effect interpretation of FLC ratio.
Methods
In this study 26 patients with progressive MM (1 – 13 prior lines of therapy) aged 65y(36-83); IgG: 13, IgA: 8, BJ: 4, NS 1, were treated with dara plus/minus velcade or revlimid at our institution; 21 with minimum follow-up 6 months. Three patients underwent ASCT.
Results
Of 26 patients with progressive MM at baseline, 24 responded (MRD-ve 35%, VGPR 35%, PR 19%, SD 4%, PD 8%) Immunoglogulin suppression; There was profound suppression of normal unaffected Ig levels at 6 months in 25/26pts inc those in CR; e.g. 7 patients with IgG myeloma on dara monotherapy ≥ 6 months; at 1 month normal IgA was reduced by 30-86% (m 80%); IgM by 25-86% (m 66%). this pattern occurred in non-IgG patients. Infections; there were 95 infection events seen including 27% URTIs (grade 3) & 1 grade 4 influenza associated death. Unaffected FLC Suppression; in 24 (of 26) patients unaffected FLCs dropped at 1 month (2 were stable), e.g. in 7 IgGk patients λ light chains had dropped from 1.3mg/L to 0.7; 6.3 to 4.9; 13.6 to 5.3; 5.9 to 1.2; 17.1 to 7.9, 10 to 6.6; 9.7 to 7.0 at 1 month. This was compared with a rise in unaffected λ light chains in 6 (of 7) of these patients 1 month into a prior (non-dara) MM therapy. ASCTs Three patients received planned ASCTs; two had PBSCs harvested following dara treatment. Pt1. F 72, IgAλ. 13 previous lines (9 yrs) treatment, 6 cycles dara pre ASCT; 10 post. ANC engraftment; 12 days. Inpatient stay (los): 14 days. Pre ASCT: MRD+ve (PP14g/L) post ASCT: MRD-ve. Pt 2. F 49, IgGk. 4 previous lines (9 yrs) treatment. 7 cycles Dara pre ASCT; 10 post. ANC engraftment 13 days. los: 15 days. MDR+ve status (BMB IP+iv) pre SCT. post MRD-ve. Pt 3. M 63 IgAλ /AL. 2 previous lines (2yrs) treatment. 7 cycles Dara pre ASCT; 10 post. ANC engraftment: 13 days. los: 22 days. MRD-ve status pre SCT; post MRD-ve. All three had serum dara levels at time of ASCT.
Conclusion
We describe profound normal immunoglogulin suppression with associated infection for patients on dara, with or without serum dara levels present. Three ASCT patients engrafted and were discharged from hospital promptly. They mobilized standard stem cell yields, had no evidence of autologous GVHD, unexpected infections, or an IRR with their next infusion of dara. The effect of dara in suppressing the unaffected FLC requires consideration when monitoring FLC ratios in these patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Autologous hematopoietic stem cell transplantation, Free light chain, Immunoglobulin, Immunotherapy
Abstract: PB2228
Type: Publication Only
Background
The anti-CD38+ monoclonal antibody Daratumumab (dara) is established as part of the treatment pathway for MM, along with autologous stem cell transplantation (ASCT) (IMWG 2017). Patients who have previously received, or are receiving Daratumumab have altered cellular inmmunological status (ASH 2017 abstract 3148)
Aims
To review suppression of normal serum immunoglogulins in dara treated patients, and possible increased infection risk (EBMT 2018 Powles et al Abstract B232), and whether this impinges on the safety of ASCT. To determine if in ASCT patients, this altered immune status, results in poor stem cell harvesting, delayed engraftment, infections, possible autologous GVHD, and dara infusion- related reactions when re-challenged post ASCT. We also look to see if suppression of normal Free Light Chain (FLC) levels occurs on dara, which may effect interpretation of FLC ratio.
Methods
In this study 26 patients with progressive MM (1 – 13 prior lines of therapy) aged 65y(36-83); IgG: 13, IgA: 8, BJ: 4, NS 1, were treated with dara plus/minus velcade or revlimid at our institution; 21 with minimum follow-up 6 months. Three patients underwent ASCT.
Results
Of 26 patients with progressive MM at baseline, 24 responded (MRD-ve 35%, VGPR 35%, PR 19%, SD 4%, PD 8%) Immunoglogulin suppression; There was profound suppression of normal unaffected Ig levels at 6 months in 25/26pts inc those in CR; e.g. 7 patients with IgG myeloma on dara monotherapy ≥ 6 months; at 1 month normal IgA was reduced by 30-86% (m 80%); IgM by 25-86% (m 66%). this pattern occurred in non-IgG patients. Infections; there were 95 infection events seen including 27% URTIs (grade 3) & 1 grade 4 influenza associated death. Unaffected FLC Suppression; in 24 (of 26) patients unaffected FLCs dropped at 1 month (2 were stable), e.g. in 7 IgGk patients λ light chains had dropped from 1.3mg/L to 0.7; 6.3 to 4.9; 13.6 to 5.3; 5.9 to 1.2; 17.1 to 7.9, 10 to 6.6; 9.7 to 7.0 at 1 month. This was compared with a rise in unaffected λ light chains in 6 (of 7) of these patients 1 month into a prior (non-dara) MM therapy. ASCTs Three patients received planned ASCTs; two had PBSCs harvested following dara treatment. Pt1. F 72, IgAλ. 13 previous lines (9 yrs) treatment, 6 cycles dara pre ASCT; 10 post. ANC engraftment; 12 days. Inpatient stay (los): 14 days. Pre ASCT: MRD+ve (PP14g/L) post ASCT: MRD-ve. Pt 2. F 49, IgGk. 4 previous lines (9 yrs) treatment. 7 cycles Dara pre ASCT; 10 post. ANC engraftment 13 days. los: 15 days. MDR+ve status (BMB IP+iv) pre SCT. post MRD-ve. Pt 3. M 63 IgAλ /AL. 2 previous lines (2yrs) treatment. 7 cycles Dara pre ASCT; 10 post. ANC engraftment: 13 days. los: 22 days. MRD-ve status pre SCT; post MRD-ve. All three had serum dara levels at time of ASCT.
Conclusion
We describe profound normal immunoglogulin suppression with associated infection for patients on dara, with or without serum dara levels present. Three ASCT patients engrafted and were discharged from hospital promptly. They mobilized standard stem cell yields, had no evidence of autologous GVHD, unexpected infections, or an IRR with their next infusion of dara. The effect of dara in suppressing the unaffected FLC requires consideration when monitoring FLC ratios in these patients.
Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical
Keyword(s): Autologous hematopoietic stem cell transplantation, Free light chain, Immunoglobulin, Immunotherapy